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A REGIONAL AND SYSTEMIC OVERVIEW OF FUNCTIONAL
NEUROANATOMY
INDIANA UNIVERSITY
SCHOOL OF MEDICINE
TERRE HAUTE CENTER FOR MEDICAL EDUCATION
MEDICAL NEUROBIOLOGYDR. WILLIAM J. ANDERSON
I. ORGANIZATION OF THE NERVOUS SYSTEM
A. THE THREE-NEURON NERVOUS SYSTEM
The human nervous system is extremely complex; it receives
and interprets all outside stimuli. it integrates information
from the outside world with that from inside the body, and it
initiates appropriate responses to the environment, including
all movements and all behavioral acts. The human central nervous
system (CNS) contains close to a trillion (1012)
neurons, and connections between these neurons approach ten
thousand trillion (1016). The connections are not
random, but are highly organized and precise. These connections
can be considered as specific systems performing specific
functions and processing specific information. The Organization
of neural tissue into systems becomes clearer if we examine the
nervous system of a primitive animal, the sponge. This will
permit a brief look at steps in the evolution of the human
nervous system.
The nervous system appears in sponges as a derivative of
the ectoderm in contact with the external environment. This
modified ectoderm responds to noxious stimuli and causes the
organism to withdraw from them. This primitive nervous system is
a one neuron nervous system in which a single type of
nerve cell receives external stimuli and initiates a withdrawal
response by initiating a contractile action in effector tissue
(Fig. 1-1). Direct contact of nervous tissue with the external
environment has persisted throughout evolution and is still
present in the human (e.g., cutaneous receptors). However, to
permit a diversity of response, the same neuron in humans that
responds to external stimuli does not directly contact effector
tissue. As the nervous system developed phylogenetically,
specialization of neural tissue into sensory neurons in contact
with the environment, and motor neurons in contact with effector
tissue, occurred. This specialization produced a two-neuron
nervous system, such as that found in some coelenterates
(Fig. 1-2). The sensory neuron in this system no longer
interacts directly with the effector tissue. Rather, the sensory
neuron conveys the stimulus to a second neuron, the motor
neuron, which then communicates with the effector tissue,
initiating a motor action in response to the sensory input. The
motor neuron is no longer in contact with the external
environment but is totally within the organism.


The direct communication between sensory input neurons and
motor output neurons has persisted throughout evolution and can
be seen in humans in the form of muscle stretch reflexes
(sometimes called deep tendon reflexes). This reflex is
initiated by applying a sensory stimulus to a muscle tendon (a
tap or stretch of the tendon with the reflex hammer). The
stretching of the muscle activates the receptor of a sensory
neuron. The sensory neuron communicates directly with a motor
neuron in the spinal cord. The motor neuron communicates
directly with the muscle being stretched and causes the muscle
to contract. The same organization of neurons that originally
evolved to allow quick response to noxious stimuli has persisted
in the human as a system that permits the unconscious regulation
and maintenance of a particular state of muscle activity.
Such a reflex mechanism, through just two types of neurons,
sensory and motor, allows little flexibility in the behavior of
the organism. Direct contact between sensory and motor neurons
permits only a contraction or non-contraction of the effector
tissue, an all-or-none response. It does not allow for a
partial, or graded, response, nor does it allow the response to
be integrated with other stimuli being received by the organism.
Advanced behavior and adaptive responses require more complex
processing between the sensory input and the motor output. This
intermediate system of information processing is made possible
by the addition of a third kind of neuron to the two-neuron
nervous system, the intermediate neuron. This final
neuronal addition to nervous system evolution is present in more
advanced animals, including humans. It is designated the
three neuron nervous system and represents the most advanced
and flexible or nervous system patterns (Fig. 1-3). The
intermediate neuron (sometimes called interneuron)
provides more processing of incoming information and allows more
flexibility in the response.

This three-neuron nervous system has reached its highest
level of development in the human brain. Specialization and
complex communication networks have expanded the role of
intermediate neurons to the point to which the entire human
brain, with the exception of a few million motor neurons
supplying muscles of the head and neck, consists entirely of
intermediate neurons. Our ability to think, write, speak, and
perform any complex action is based upon the functioning of
them. These intermediate neurons are not in direct contact with
either the external environment or the effector tissue but are
clustered together into a complex central network--the CNS.
As complex as the human nervous system is, it can be broken
down into basic components for study. The human nervous system
can be thought of as having two basic parts: (1) a peripheral
nervous system (PNS) that is in contact with the external
and internal environment; and (2) a central nervous system
(CNS) that is responsible for processing information and
providing an appropriate response to the environment. The PNS
has a somatic component consisting of sensory input (sensory
receptors and neurons) and motor output (axons and the
neuromuscular junction of motor neurons) that was classically
described as controlling the contraction of skeletal muscles.
The PNS also has an autonomic component that controls smooth
muscles, cardiac muscle, and secretory (or exocrine) glands,
allowing for the continuous regulation of both basal homeostatic
and stress-related functions of the body. More recent evidence
shows many other targets of the autonomic nervous system such as
hepatocytes, brown fat cells, and cells of the immune system
within lymphoid organs. This autonomic nervous system (ANS)
is further subdivided into two components, the sympathetic
nervous system (SNS) and the parasympathetic nervous
system (PsNS). The sympathetic component is a widespread
system that responds to stress or a demand for activity by
causing a general arousal and readiness of the body to cope with
the perceived situation, often called a "fight or flight"
response. The parasympathetic component is responsible for the
control of homeostatic functions necessary for the well being,
basic maintenance, and repair of the body. An example of PsNS
function is normal digestion. A third subdivision of the
autonomic nervous system, the enteric nervous system, consists
of approximately 100 million neurons within the gut, many of
which are autonomous, not in contact with parasympathetic or
sympathetic neurons.
The CNS is composed of a brain and a spinal cord. The
spinal cord receives axons of sensory neurons bringing
information into the CNS from the body. It also contains the
cell bodies of the motor neurons whose axons leave the spinal
cord to innervate skeletal muscles of the body. The bulk of the
spinal cord is made up of interneurons that mediate incoming
sensory information and outgoing motor and autonomic
information, and fiber tracts that represent ascending and
descending communication channels interconnected with higher
structures in the brain. The brain can be divided into a
brain stem and a forebrain. The brain stem has three
basic anatomical subdivisions continuing upward (rostrally) from
the spinal cord. These are the medulla, the pons,
and the midbrain. The cerebellum is a large
convoluted structure derived from the pons but associated with
all three of the other subdivisions that has a major role in
smoothing and coordinating motor activity. The medulla, pons,
and cerebellum are parts of the rhombencephalon, while
the midbrain is synonymous with the mesencephalon. The
brain stem receives sensory input from general and special
sensory systems of the head and neck and contains motor and
central autonomic neurons supplying the head and neck, and
portions of the viscera. In this manner, the organization of the
brain stem is similar to that of the spinal cord. In addition,
the brain stem contains mechanisms and structures for more
sophisticated sensory, motor, and autonomic processing that are
capable of integrating and coordinating more complex activities
(e.g., respiratory rhythm, control of body tone, eye movement
responses to head position). The forebrain (prosencephalon)
can be divided into a diencephalon, including mainly
the thalamus and the hypothalamus, and a telencephalon,
including the olfactory system, the limbic system,
the basal ganglia (corpus striatum), and the neocortex.
The functional role of these higher centers of the brain
will be discussed later in this chapter.
In addition to the organization of neuronal structures of
the brain, the study of the nervous system must also include its
coverings, the meninges, and two fluid systems, the blood
supply and the cerebrospinal fluid. The meninges comprise three
layers of membranes covering the brain.
The innermost layer, the pia, adheres very closely
to the surface of the brain and follows all of the convolutions.
The second layer, the arachnoid, encloses both the
subarachnoid space, which contains the CSF, and the arteries and
veins supplying the cortex; it stretches across the sulci
without following the folds. The third or outer layer, the dura,
is a tough protective membrane; itself composed of two layers
(Fig. 1-4). Major venous sinuses that drain blood from the brain
lie between its two layers. The outermost layer is tightly
adherent to the bones of the skull.

The blood supply to the brain comes from two sources: (1) two
vertebral arteries that unite to form the basilar artery on the
ventral midline surface of the pons, supply most of the brain
stem: and (2) the internal carotid arteries supply most of the
forebrain. The two arterial systems are connected at the base of
the brain by communicating branches, the anterior and posterior
communicating arteries, forming the circle of Willis
(Fig. 1-5). The venous blood drains into the major venous
sinuses through superficial and deep veins. The sinuses then
drain into the internal jugular veins. The cerebrospinal
fluid (CSF), found in both the subarachnoid space and the
ventricles within the brain, is an ultrafiltrate of blood. CSF
is produced by the choroid plexus from arterial blood and by
leakage of the extracellular fluid into the ventricular cavities
of the brain. The CSF circulates through the ventricular system
(from lateral ventricles of the forebrain, into the third
ventricle of the diencephalon, into the aqueduct of the
midbrain, and into the fourth ventricle of the rhombencephalon),
escapes into the subarachnoid space through foramina (the
foramen of Magendie in the midline and the lateral
foramina of Luschka) at the caudal end of the fourth
ventricle in the medulla, circulates around the external surface
of the brain and spinal cord in the subarachnoid space and its
enlargements, called cisterns, and is absorbed into the
venous blood through specialized one-way valve structures of the
arachnoid, the arachnoid villi. The CSF provides a
hydraulic cushion to protect the brain from contact with the
hard bone of the skull and may provide a communication channel
for CSF-borne substances to influence neurons.

The foregoing discussion provides a very general plan of the
nervous system. Understanding the nervous system requires
knowledge of how the neuron functions and how groups of neurons
function together as systems. The characteristics and properties
of the neuron will be discussed next. The nervous system itself
can be organized and studied in two different but complementary
ways, regionally and systemically. Both of these organizations
will be used to provide a framework for study. The PNS,
including both somatic and autonomic components, will be
discussed first, followed by a regional overview of the central
nervous system. Finally, the nervous system will be studied
longitudinally, according to functional systems.
II. NEURONS AND SUPPORTING CELLS
1. The Neurons
a. Morphological Characteristics of Neurons
The neuron is the fundamental unit of the nervous
system. Its function is to communicate coded information over a
distance. That distance may be very short, as with a local
interneuron, or very long, as with a motor neuron whose cell
body is in the spinal cord and whose axon terminates on a muscle
of the foot. The neuron achieves this conduction of information
by carrying an electrical potential down its axon. The shape of
the neuron is particularly conductive to the transport of
information. Typically, the cell body (soma) has two
kinds of processes, called neurites, extending from it.
Dendrites are extensions of cytoplasm from the cell body
that generally are considered to receive information from other
neurons and pass that information toward the cell body (Fig.
1-6). The branching patterns of dendrites may be very
distinctive, reflecting the type and amount of information that
a specific process received; these dendritic arborizations can
range from sparse and small (only a few microns), or elaborately
branched and huge, extending over millimeters of distance. The
second type of neurite is the axon. It usually originates at the
cell body (or primary dendrite) and is a long process of
constant diameter through which the neuron communicates with
other neurons or effector structures. Each neuron has at most
one axon leaving the cell body or a dendrite, but that axon may
branch to form many processes called axon collateral’s,
each of which may communicate with different parts of the
nervous system. In its course of travel, the axon may give rise
to many small bulges called axon terminals (also called
boutons or varicosities). The terminal is in close
proximity either to another neuron or to the effector tissue in
the case of the outflow of the PNS. This gap between one neuron
and another, or between neuron and effector tissue, is called a
synapse. The flow of electrical information in a neuron
is generally from the dendrites to the cell body, and then down
the axon to the terminals, carrying the message toward the next
neuron in that chain of communication, or toward the effector
tissue. Figure 1-6 shows a schematic representation of the basic
neuron and a few examples of neurons with specific shapes.

The form and structure of each neuron reflects the role of
that neuron. Very specific connections exist between neurons,
establishing communication channels that may extend over long
distances and may be composed of a chain of many neurons. The
anatomy of these communication channels, called neuronal
connections or projections, determines the
hierarchical relationships and influences that one neuron
population exerts over other neurons. A knowledge of these
connection patterns is essential for the adequate evaluation of
neurological disorders and their therapy. For example, a spinal
cord injury removes motor neurons from the control of higher
centers in the brain by severing or damaging descending
pathways. Removal of this control, which normally holds these
neurons in check and regulates their response to incoming
sensory stimuli, results in hyperexcitability and
over-responsiveness (called release phenomena, or
disinhibition) of spinal cord lower motor neurons (LMNs) to
certain types of stimuli, manifested in the patient as
spasticity. A knowledge of which connections were destroyed and
which connections remain intact provides a rational basis for
the therapy of such a patient.
b. Electrical Properties of Neurons
Understanding how neurons transfer information and how that
information can be altered by outside influences can help to
explain the mechanisms by which groups of neurons act together
as integrated systems. The neuron has two properties that allow
it to transfer information, conductivity and
neurotransmission. The neuronal cell membrane is an
excitable membrane; it is capable of conducting an electrical
impulse over a distance. Because of the ionic balance that
exists between the cytoplasm of a neuron and the extracellular
fluid, based upon the differentially permeable neuronal
membrane, an electrical potential, called the resting
potential, exists across the cell membrane. The resting
potential is produced by the properties of the neuronal membrane
itself, particularly the differential permeability of the
membrane to sodium (Na+) and potassium (K+)
ions, and the metabolic pumps that help to main the unequal
distribution of these ions. The resting potential is normally a
voltage of approximately -70 to -80mV. Excitation or inhibition
of the membrane causes the potential to change. If an excitatory
stimulus is strong enough to allow the membrane potential to
reach a higher specific voltage, called the threshold,
the neuron fires an action potential. The action potential
represents a specialized way of conducting an electrical
impulse over a long distance, the entire length of the axon,
without dying out. That is to say, the action potential is
non-decremental (does not decrease in amplitude) over the length
of the axon, even a meter or more. The action potential occurs
because of a rapid increase in sodium conductance through the
sodium channels that is brought about by a stimulus that
depolarizes the membrane to threshold, thereby opening the
sodium channel and permitting the sodium ion to move across the
membrane. The resultant depolarization, in turn, increased the
potassium conductance, thus permitting potassium to move out of
the axon, restoring the axoplasm. to a polarized state. The
sodium and potassium ions then are moved out of, or into the
axon, respectively, by energy dependent ion pumps. The action
potential is propagated down the axon by re-initiation at each
adjacent increment of axon, or at each bare site of a myelinated
axon (node of Ranvier); a process called saltatory
conductance because the action potential appears to skip
from node to node. The reinitiating of the action potential is
brought about by current flow along and within the axon that
brings the next node or next patch of axon membrane to
threshold. The action potential is in contrast graded
potentials, small changes of the membrane voltage away from
the resting potential in either direction, that will decay or
die out after a short distance if it does not reach threshold,
and will diminish with time. In general, dendrites and cell
bodies carry graded potentials, while action potentials are
carried by axons. The graded potential allows a great deal of
flexibility in processing in the nervous system because it can
be summed. In contrast to the action potential that, if it
fires, is always a constant amplitude and velocity for a given
axon. The graded potential may be increased by several inputs
arriving at the neuron at the same time (spatial summation)
or by individual inputs that act on the membrane
repetitively, before the resultant graded potential has had an
opportunity to die out (temporal summation). This means
that increasing the input to a given neuron can bring it to
threshold and cause it to fire an action potential, or that an
input can bring a neuron to a more excitable state; closer to
threshold for firing an action potential, even though that input
itself does not cause an action potential directly (called
subliminal excitation). It also means that if one
form of input is lost due to injury or disease, resulting in a
failure of a given population of neurons to function, those
neurons may then be caused to fire by increasing the input from
another source. This principle is the basis for therapy of some
disorders.
Neurotransmission
When an action potential reaches an axon terminal or
a varicosity, it causes the membrane potential of that terminal
to increase (i.e., to go from -70 mV toward 0). This change
reduced the negativity of the potential across the membrane and
is called depolarization. Depolarization of the nerve
terminal results in the release of a chemical messenger called a
neurotransmitter. The release of neurotransmitter depends
on the presence of calcium ion (Ca++), which enters
the cell during depolarization and permits the release of the
neurotransmitter from the cytoplasm or from the prepackaged
subcellular compartment, the synaptic vesicle, by a process
called excitation-secretion coupling. The vesicles in most
terminals’ range from 20-100 nm in diameter, contain the
neurotransmitter, can combine with the nerve terminal membrane
in the presence of Ca++, and release the transmitter
into the synaptic cleft. The vesicle membrane is recycled later
(Fig. 1-7) by a process of pinocytosis (pinching off a
membrane). The membrane of the axonal terminal pinches off
fuzzy-coated vesicles inside the terminal, which then merge to
form a cisternal apparatus. This apparatus then pinches off
recycled synaptic vesicles, ready for use again in the process
of neurotransmission. The interaction of a
neurotransmitter with its receptor (a surface protein) causes a
change in the membrane of the target cell, initiated through a
second messenger such as a cyclic nucleotide. The change can
cause (1) a decrease in the potential difference or voltage
across the cell membrane (making it more positive), called a
depolarization, or (2) an increase in the potential
difference across the cell membrane (making it more negative),
called hyperpolarization. Both these post-synaptic
potentials (PSPs) are graded potentials and can be summed. A
depolarization raises the potential toward the threshold, making
it easier for the cell to fire an action potential. If a single
depolarization is strong enough or if enough depolarization’s
occur, threshold may be reached and the neuron will fire an
action potential. A hyperpolarization, on the other hand, lowers
the potential away from the threshold, making it more difficult
to fire an action potential. If a neurotransmitter (ligand)
-receptor interaction cause the depolarization of the cell
membrane, it is excitatory, and the neurotransmitter stimulating
it is called an excitatory neurotransmitter, and the
synapse is considered an excitatory synapse. If a
ligand-receptor interaction causes a hyperpolarization of the
target cell membrane, it is inhibitory, and the neurotransmitter
stimulating it is called an inhibitory neurotransmitter.
This synapse is an inhibitory synapse. Recent evidence has shown
that a single terminal may contain more than one
neurotransmitter (for example, a catecholamine and a peptide),
so this simplistic scheme of excitatory and inhibitory neurons
may require extensive modification.

A nomenclature problem has developed as neurotransmitter
research has demonstrated that a neurotransmitter can be
excitatory at one kind of synapse and inhibitory at another.
This seeming paradox is easily explained if it is realized that
the single factor which determines whether the transmitter is
excitatory or inhibitory is the receptor on the target cell, not
the transmitter itself. The target cell membrane may possess
receptors for many neurotransmitters
The evolution of chemical transmitters interacting with
specific receptors provides the nervous system with additional
flexibility in the processing of information. The neuron can sum
information received from different sources, received at
different rates, and received from both excitatory and
inhibitory sources, and can integrate it to provide a single
response based on the processing of a large amount of diverse
information. It should be noted that other chemicals besides
neurotransmitters might interact with receptors. Various drugs
exploit an interaction with receptors in order to restore
function when there is a lack of transmitter released, when the
releasing neuron has been damaged, or when it is necessary to
block the release or activity of a transmitter present in too
high a quantity. These receptor interactions, whether excitatory
or inhibitory, can be used to treat numerous disease states,
such as Parkinson's disease, depression, and spasticity.
d. Patterns of Neuronal Connections and Interactions
Additional flexibility in information processing is brought
about by diverse patterns of connections between
neurons. The axon of one neuron may synapse with the dendrites
of another neuron. This type of synapse is called an
axo-dendritic synapse. Other types of synapses can occur,
such as axons synapsing on cell bodies, called axo-somatic
synapses; axons synapsing on axons, called axo-axonic
synapses, dendrites synapsing on dendrites, called
dendro-dendritic synapses, and so forth. Figure 1-8
illustrates the synaptic patterns just described. Because
dendrites and cell bodies usually carry only graded potentials
that may die out, it seems logical that synapses on these
structures, especially if they are far from the axon, are less
likely to lead to an action potential than a synapse near the
origin of the axon. Synapses closest to the point at which the
axon leaves the cell body, called the axon hillock (Fig.
1-6), or on the initial segment of the axon, appear most likely
to cause the firing of an action potential because the action
potential originates at this point. A similar situation exists
with inhibitory synapses. However, recent evidence suggests that
a synapse on a distal dendrite may exert a greater influence on
the excitability of the hillock region than geometry alone would
predict due to variability in the membrane resistance.


Of particular interest is the axo-axonic inhibitory synapse
on the axon terminal. It is a highly effective way of preventing
the axon's action potential from releasing neurotransmitter at
the axon terminal. If the terminal does not release its
neurotransmitter(s), no message is communicated farther along
the neuronal chain, even though an action potential did fire
initially, and propagate down the axon. This phenomenon, called
presynaptic inhibition, depends upon an axo-axonic
synapse, brought about when a neurotransmitter from the afferent
axon terminal acts upon receptors on the second (post-synaptic)
terminal, depolarizing it and preventing neurotransmitter
release even when the action potential invades that terminal.
Using a combination of excitatory and inhibitory synapses,
sophisticated neuronal chains of control can be established. For
example, Figure 1-9 illustrates a chain of three neurons. Each
of the three neurons are excitatory, as indicated by the open
cell body (closed cell bodies indicate inhibitory neurons). If A
receive a stimulus, it can excite B, which can excite C, which
will excite the target tissue, T. In Figure 1-10, an inhibitory
neuron has been introduced at B. A stimulus exciting A causes A
to excite B. B, however, inhibits C and prevents it from firing.
The target tissue therefore is not excited. Figure 1 - 11 adds a
further complication. Both A and B are inhibitory. A will
inhibit B and prevent it from inhibiting C. If C can receive an
excitatory input from another source, or if it can fire
spontaneously, the target tissue will be excited. This process
of removing an inhibition is called disinhibition (or a
release phenomenon). Disinhibition can occur when a previously
inhibitory neuron is damaged, or when another inhibitory neuron
inhibits the firing of the original inhibitory neuron. This
happens in many motor disorders, such as spasticity, athetosis,
and other involuntary movement disorders.

One more example of the possibilities of neuronal control
mechanisms illustrates the process of feedback inhibition.
Figure 1- 12 shows neuron A exciting neuron B, which in turn
excites the target tissue. However, an axon collateral from
neuron B excites an inhibitory interneuron, C, which inhibits
the firing of neuron A, causing the system to be shut off. It is
clear from the foregoing discussion that neuronal control
mechanisms can become very complicated and can involve chains of
dozens, or perhaps even hundreds of neurons. There are other
examples of neuronal control that will be discussed with the
systems in which they are active.
2. Neural Response to Injury and Manipulation
The foregoing discussion can aid in the understanding of
the manipulations that can be performed on a damaged or
defective nervous system. Generally, neurons are not capable of
replication in the adult brain, and only certain kinds of small
neurons are still able to replicate during neonatal development.
A dead neuron cannot be replaced or regenerated by cell
division, in contrast to other organs such as liver or skin that
can heal with new, functional cells. When a neuron is destroyed,
its specific functions are permanently lost. When a neuron is
damaged, it may cease to function altogether for a period of
time, it may undergo a period of suboptimal or diminished
function, it may totally recover its function and perform
normally, or it may function in a hyperexcitable and excessive
manner (producing seizure activity). If an axon is damaged in
the PNS, regeneration of the distal portion of the axon may
occur, accompanied by readjustments of metabolism by the cell
body, a process called central chromatolysis. If an axon
is damaged in the CNS, it is unlikely that appropriate
regeneration of that axon or complete restoration of that
function will occur. In the CNS, neuronal damage or cell loss
can result in an anatomical and functional reorganization of
remaining, intact neurons, but not the destroyed neurons. When a
specific input to a particular neuron, such as a motor neuron,
is lost, as occurs in spinal cord injury, remaining neurons in
the spinal cord or the dorsal root ganglion cells that are not
damaged can sprout additional axonal terminals to reinnervate
the partially denervated neuron. Neurons may be facilitated
therapeutically to assume wider functional roles, such as when
vestibular neurons are manipulated to influence motor tone in a
cortically damaged patient. Perhaps neurons also may be
manipulated therapeutically to assume new functional roles.
The limitations of therapy in neurological dysfunction must
be understood clearly. The available therapeutic approaches,
some occurring naturally and some aided by a neurologist or
therapist, include the following: (1) reinnervation and
restoration of function in the PNS due to regeneration,
generally achieved by nature, or aided by microsurgical
reanastomoses of severed nerve fascicles; (2) recovery of
function of neurons that have been temporarily but reversibly
damaged, such as may occur in a stroke; (3) manipulation or
stimulation of an intact system to overcome an imbalance
produced by damage to another system (for example, use of
vestibular manipulation to alter postural tone in a cortically
damaged patient, or administration of an anti-cholinergic drug
to counterbalance the loss of a dopaminergic system in
Parkinson's disease); (4) manipulation (stimulation or
inhibition) of a reorganized or reorganizing system following
neurological damage (for example, training or eliciting reflex
responses for bladder emptying or for sexual function following
a spinal cord injury); (5) drug manipulation of intact neurons
through alterations in neuronal metabolism, neuronal
communication, or neuronal excitability, often through use of
agents directed towards specific receptors; (6) surgical
intervention to remove a mass, to restore a balance of
functions, to alleviate pain temporarily, or to alter the
hormonal milieu of the nervous system; and; (7) transplantation
of neurons or other neurotransmitter-producing cells (e.g.
adrenal medulla) into a damaged adult brain.
Autotransplantation of adrenal medullary chromaffin cells
into the striatum of patients with Parkinson's disease already
has been attempted in humans at several medical centers. The
results have been equivocal. It is not yet known whether these
systems, if they do provide any benefit to the patient, act
through the release of a neurotransmitter, through release of a
trophic agent, or only appear to have a beneficial role because
of lesion-induced effects from the considerable trauma of
surgical transplantation, or from a placebo effect and the added
attention such a patient receives. On the other hand, the
transplantation of fetal dopamine neurons into the striatum of
drug-induced Parkinsonian African green monkeys has shown a
remarkable degree of recovery from severe movement impairment.
Thus, the use of transplanted cells into brain circuitry has
considerable promise, but the underlying mechanisms, even in
experimentally successful models, is only poorly understood. The
future role of such therapy in the treatment of human
neurological deficits still requires careful evaluation because
of scientific, ethical, and social hurdles that must be
overcome.
An additional approach to therapy involves altering
neuronal functioning by environmental and other intangible
influences not often viewed as part of current therapy for
neurological disorders. Significant improvement of a patient's
condition due to emotional and motivational factors is a real
phenomenon and may exert a powerful influence on the progress of
a neurological damaged patient. While the neuroscience’s cannot
yet explain how these mechanisms work, or how emotional and
cognitive factors interact in recovery from neurological
disease, the empirical recognition and utilization of these
phenomena is not to be overlooked. In some neurological
conditions, the concern, determination, friendship, or empathy
of the family and the medical staff may be equally as important
as the actual physical or medical benefits of therapy. It is
admittedly difficult to teach a physician or therapist how to
persist in the face of overwhelming odds; how to truly care for
the emotional well-being of a debilitated elderly patient; or
how to empathize with the hurt, the uncooperative, or the
unlovely, but those who possess such capabilities should be
given encouragement.
3. Supporting Cells
Neurons are supported by non-excitable cells, called
glia in the CNS, and Schwann cells in the PNS.
These cells help to insulate, separate, and protect neurons and
may assist the neurons metabolically. These cells respond to
injury by forming scar tissue and by phagocytosis of debris. In
the CNS the glia are of three types: astrocytes,
oligodendroglia, and microglia. In addition,
supporting ependymal cells line the ventricles of the brain and
separate the cerebrospinal fluid (CSF) from the substance of the
brain.
Astrocytes are responsible for forming scar tissue
in response to injury. Within a week of the initial injury,
astrocytes begin laying down fibrous processes that fill in
spaces left by the injury, and add strength to the areas of
necrosis and damage. Unfortunately, the astrocytic scar tissue
also can form an irritating focus that can initiate seizure
activity. Astrocytes also send endfeet (processes with
bulbous endings) to contact the basement membranes of
capillaries in the brain. Although tight junctions between
adjacent cells linking the blood vessels exclude certain
substances from the brain and form the cellular basis for a
blood-brain barrier, the astrocytic endfeet may play a secondary
role in the barrier by sequestering products, guarding the
extracellular space, or inducing enzymes in the endothelial
cells. Astrocytes also separate nerve cell bodies and processes
by physically sending astrocytic processes between them.
Astrocytic endfeet also form a layer of contact with the pia
(pial glial membrane) as a protective covering of the brain.
Recent evidence suggests that astrocytes may provide support to
neurons through regulation of the ionic milieu (sequestration of
potassium), or may produce active substances that can interact
with neurons directly (e.g. production of interleukin. In
addition, astrocytes also appear to posses the capability to act
as antigen-presenting cells, when their major histocompatibility
(MHC) antigens are up regulated in the presence of gamma
interferon from lymphocytes. These cells may play a roll in the
immunological protection of the CNS.
Oligodendroglia are responsible for myelinating the axons
of central neurons. Myelin is formed by the concentric wrapping
around an axon of an oligodendroglial process that was formed
from its cell membrane. The cytoplasm in the oligodendroglial
processes is squeezed out during the wrapping, causing the
membranes to abut each other, and forming a lamellar arrangement
of wrapping around the axon. Myelin, which forms during fetal
development through adolescence, is essential for normal nerve
function. Its main purpose is to permit an increased speed of
electrical conduction of the action potential down the axon.
Proper speed permits accurate neuronal functioning. Any
demyelinating disorder such as multiple sclerosis, or
interference with normal myelination, results in slowed
conduction velocity and incompetent functioning of the affected
axons.
Microglia are small phagocytes found in CNS in response
to an injury. They are the first glial cells to arrive at the
injury and are found in abundance at the site for at least a
week. As debris is removed, astrocytes move in and lay down
fibrous scar tissue. A major task of microglia is removal of
debris in the CNS. Some microglia in the CNS appear to be of
mesodermal origin, from the periphery, and probably are invading
macrophages. Other evidence points to an origin for some
microglial cells from neuroectoderm. Microglia also may
be able to present antigens and functionally immunologically in
the CNS.
Schwann cells are the supporting cells in the PNS.
Their major functions are to separate, insulate, and myelinate
axons. All peripheral axons have at least one layer of Schwann
cell cytoplasm, called a Schwann sheath, surrounding
them. Larger axons (greater than 2 um) will have a complete
myelin sheath formed from many concentric layers of Schwann cell
membrane. Schwann cells also can respond to injury or to a
degenerative process such as demyelination by
phagocytosis of debris. They then can divide and form new cells,
which will remyelinate the axon. A Schwann cell can myelinate
only one segment (one millimeter or so) of one peripheral axon,
in contrast to oligodendroglia, which can myelinate one segment
of many different central axons.
C. PERIPHERAL NERVOUS SYSTEM
1. Components
The extent of the peripheral nervous system (PNS) is
easiest to define by exclusion: it comprises all the neural
elements not in the brain and spinal cord. Because primary
sensory, motor, and autonomic elements all are connected with
the central nervous system (CNS), each has a peripheral as well
as a central component. The peripheral components can be
subdivided into somatic and autonomic portions in the following
manner.
a. Somatic Component
1. Sensory component, including receptors, primary
sensory axons and primary sensory cell bodies (found in the
dorsal root ganglia).
2. Motor component, including the axons of lower motor
neurons (LMNs) and the neuromuscular junction.
b. Autonomic Component
1. Sympathetic component, including preganglionic axons,
ganglion cells, and their postganglionic axons.
2. Parasympathetic component, including preganglionic axons,
ganglion cells, and their postganglionic axons.
2. Gross Anatomy of the PNS
There are two kinds of peripheral nerves, spinal nerves
and cranial nerves. There are 31 pairs of spinal
nerves. These are all mixed nerves containing more than one of
the aforementioned sensory, motor, or autonomic components to
the body. The cranial nerves supply these same functional
components to the head and neck. The only difference, other than
their area of supply, is that the individual cranial nerves are
more specialized. Some of them are almost purely sensory, some
are purely motor, and some are partially autonomic. Spinal
nerves distribute to the body in a fairly regular pattern
(called somatotopic distribution), based on their origin from
the spinal cord. The 31 spinal nerves are distributed as
follows: 8 cervical, 12 thoracic, 5 lumbar, 5 sacral, and 1
coccygeal.
The cervical nerves leave the spinal canal through the
vertebral foramina rostral to their respective vertebrae except
for cervical nerve 8, which leaves caudal to vertebra 7 (because
there are only 7 cervical vertebrae). The rest of the spinal
nerves leave the vertebral column caudal to their vertebrae.
These nerves are numbered for their vertebral levels in the
following manner. The first cervical nerve is designated C1, the
second, C2, and so forth. The first thoracic is T1; the third
lumbar is L3. The cervical nerves supply the shoulder and the
upper limb. The thoracic nerves supply the body trunk in the
thoracic and abdominal region. The lumbar and sacral nerves
supply the lower limb and perineal region. Figure 1- 13 shows
the spinal nerves as they exit from the vertebral column.
Cranial nerves are designated by Roman numerals I through XII
as well as by their individual names. Because their areas of
distribution and their functions are not as regular as the
spinal nerves, a brief summary has been provided in the section
of this chapter on Regional Neuroanatomy (Table 1-4). These
cranial nerves have been subdivided into their sensory, motor
and autonomic components. For a more complete and detailed
review of these nerves as well as the precise distribution of
the individual spinal nerves, one of the neuroanatomy textbooks
should be consulted. Such detailed consideration is beyond the
scope of this overview. Even though cranial nerves I (olfactory)
and II (optic) have been included in the summary, they are
really peripherally located tracts of the CNS, and should be
considered part of the brain.

3. Sensory Aspects of the PNS
There are many kinds of sensory receptors, but they
all have one thing in common- they all act as transducers to
convert various types of external stimuli into electrical
impulses. We will not describe the anatomy of these receptors
because we are more concerned here with the kinds of information
they can transform. For a detailed recounting of receptor
anatomy, consult one of the major neuroanatomy textbooks. Bear
in mind that there is still no absolute correlation of
morphological receptor types and the functional transduction
they perform for specific modalities. For the body, these types
of information (modalities) can be arranged as follows:
a. Epicritic Modalities (Somatic Sensation)
- Fine, discriminative touch, vibration, two-point
discrimination, stereognosis (the ability to determine the
size, shape, and texture of an object by tough alone)
- Proprioception, information concerning the action and
position of muscles and joints
- (a) Conscious proprioception-joint position
- (b) Unconscious proprioception-muscle position and
movement
b. Protopathic Modalities (Somatic Sensation)
- Pain (both fast, localized pain and slow, excruciating,
poorly localized pain)
- Temperature
- Light moving touch
c. Special Senses
- Vision
- Olfaction
- Audition
- Vestibular proprioception, the position of the head in
space (linear and angular acceleration)
- Taste
d. Visceral Sensation
- Painful sensation from the viscera
- Non-painful sensation from the viscera
Information
transduced by the receptor is conveyed into the
CNS by a
primary sensory axon. Its most distal
part is the receptor and the initial segment immediately
adjacent to the receptor. The initial segment is the portion of
the axon in which the action potential is initiated, analogous
to the axon hillock, except that it is not next to the cell
body. The receptor functionally can be considered a
dendrite.
The rest of the
neurite can be considered the axon, which continues
into the spinal cord as part of a spinal nerve. The cell body of
the primary sensory neuron for somatic sensation is in the
dorsal root ganglion, near the spinal cord. It does not have a
direct role in carrying or initiating the action potential. The
primary sensory cell body therefore serves mainly a
trophic role to help nourish and
maintain the process. After the axon passes through the dorsal
root ganglion, it enters the spinal cord through the dorsal
root. See Figure 1- 14 for a
summary of the anatomy and connections of a primary sensory
neuron. The central processing of the information conveyed by
the primary sensory neurons will be discussed in more detail
under the sections of spinal cord and sensory systems.

4. Motor Aspects of the PNS
The only component of the motor system found in the
periphery is the axon of the lower motor neuron
(LMN). Cell bodies of
LMNs are
found in the spinal cord anterior horn (anterior horn
cells) and in motor cranial nerve nuclei in the brain
stem. The axon leaves the CNS with
a cranial nerve, or with a spinal nerve after exiting through a
ventral root. LMNs
innervate skeletal muscle. Each motor axon
innervates more than one muscle fiber and establishes a
functional motor unit (the
LMN and all muscle fibers it
supplies). When the axon carries an action potential to the
terminals, all fibers of the motor unit contract together. In
conditions in which
LMNs are damaged or
degenerating, aberrant discharges in
LMNs lead to motor unit
twitches (fasciculations),
which can be visualized directly. The junctional complex, or
synapse, between a
LMN and the muscle is called a
neuromuscular junction
(NMJ),
and the terminal of the
LMN is called a motor end
plate.
An action
potential arriving at the terminal of a
LMN
depolarizes the terminal, causing the release of the
neurotransmitter acetylcholine
(ACh). ACh
diffuses across the synaptic cleft, which in the case of the
neuromuscular junction is thrown
into numerous secondary folds, thus expanding the surface area
of muscle membrane possessing receptors with which the
ACh will
interact. ACh combines with
specific receptors on the muscle membrane, causing it to
depolarize, resulting in muscle
contraction. These ACh receptors
can be activated by nicotine, and are called nicotinic
(N)
cholinergic receptors. In the total absence of
ACh or other compounds that would
bind with the receptor, the muscle will be unresponsive and
flaccid. This is also true if the LMN
itself is destroyed so that no
neurotransmission can take place. The
cholinergic receptors on the muscle
also respond to destruction or cutting of the nerve. Normally,
receptors are concentrated densely at the
NMJ. When the nerve is lost, the nicotinic receptors
proliferate across the surface of the muscle, where they are
sensitive to ACh or
cholinomimetic compounds from any
source. Muscle twitches in this circumstance are not the result
of normal neurotransmission from an
intact nerve, but reflect the
denervation hypersensitivity of the receptors. These
twitches, called fibrillation’s, cannot be observed
visually, but can be detected by electrical recording, called
electromyography.
ACh is removed from the
synaptic cleft and is broken down by the enzyme
acetylcholinesterase
(AChE), found also on the muscle
membrane and in the motor terminals. It is extremely important
for normal nerve function that this enzyme be present and that
it break down (hydrolyze) ACh. If
it is not present and functioning properly, or if this enzyme is
inhibited by an anti-cholinesterase
agent (e.g. nerve gas), the
ACh persisting at the
NMJ will cause continued
stimulation of the nicotinic receptors and continued contraction
of the muscle that is no longer under complete
neural control. With prolonged
persistence of ACh in the cleft,
the muscle membrane is chronically
depolarized, resulting in total muscle paralysis and
death.
Certain drugs have been developed that can be used to augment
the action of ACh. For example, in
the disease myasthenia
gravis,
there are not enough receptors available to interact with the
ACh that is released from the motor
end plate because of antibodies against the nicotinic
ACh receptors. A drug that blocks
the action of AChE, called an
anti-cholinesterase (or
cholinesterase inhibitor) is given
so that the transmitter can persist in the synaptic cleft
longer, increasing the chance that it will combine with
receptors and will augment muscle contraction. It should be
clear that manipulation of the
neurotransmitter (its synthesis, release, combination
with a receptor, or its removal from the synapse and eventual
metabolism) could be extremely important in controlling muscle
activity. It also should be clear that without the presence of a
LMN, the skeletal muscle can’t be
made to function properly, or to respond to commands from the
CNS, no matter how much of a drug
or manipulative therapy is used. Fortunately, peripheral nerves
have the capacity to regenerate and repair themselves to
some extent, if the cell body has not been destroyed. In
addition, other LMNs may be able to
sprout and reinnervate
muscles previously denervated, as
happens in polio when the polio virus destroys some, but not
all, LMNs. However, when the cell bodies have been destroyed, as
in polio with total death of LMNs,
or a spinal cord crush injury at the level of total destruction,
the neurons die and are not replaced. In these cases, no amount
of treatment will help muscle tone or will restore even a small
degree of movement.
5. Autonomic Aspects of the PNS
In general, the autonomic nervous system exists as a
two-neuron chain. The first neuron has its cell body in the
CNS and is called the
preganglionic cell. Its axon, the
preganglionic axon, is
myelinated, leaves the
CNS, and synapses in an autonomic
ganglion. The ganglion contains cell bodies for the second
neuron is called the postganglionic
neuron. The postganglionic
axons are mainly
unmyelinated. The autonomic nervous
system has two divisions, the sympathetic and the
parasympathetic, which will be discussed separately.
a. Sympathetic Nervous System
The general action of the sympathetic nervous system is to
activate or arouse the organism to prepare for "fight or flight"
activity. The response of this system is widespread, preparing
the whole body for activity. It usually is activated by the
perception of stress and is not so much a reaction to a specific
stimulus as a reaction to the nervous system's interpretation of
that stimulus. It is particularly important for a therapist to
realize that a patient may respond to therapeutic manipulation
intended to assist in motor activities as if it were stressful.
The resultant activation of the sympathetics, with the
concomitant tensing of muscles, increase in heart rate and
respiration, and decrease in homeostatic mechanisms such as
digestion may be undesirable, and may interfere with therapy.
natomy of the sympathetic nervous system reflects its widespread
effects. The preganglionic cell
bodies are located in the spinal cord intermediate gray (Fig. 1-
15) of segment T1 through
L2, also called the
thoracolumbar region. These
cell bodies often are described as residing in the lateral
horn, or intermediolateral
cell column. However, recent evidence has demonstrated the
presence of additional preganglionic
sympathetic neurons in the medial regions of intermediate gray
and in the dorsal commissural gray
just above the central canal. The sympathetic
preganglionic
axons leave the spinal cord, and travel with the
LMN axons
through the ventral root to sympathetic chain ganglia
(paravertebral ganglia) that are
attached to the spinal nerve near the vertebral column. The
chain ganglion attaches to the spinal nerve by
rami
communicantes. The white ramus
communicans
(distal) contains myelinated
preganglionic
axons entering the ganglion, while the gray
ramus
communicans (proximal) contains
unmyelinated postganglionic
axons leaving the ganglion. There
is a sympathetic chain ganglion for almost every spinal nerve,
even though only the TI to
L2 segments of spinal cord have
preganglionic: sympathetic cells.
This occurs because while some of the
preganglionic axons synapse
on postganglionic cells located in
the chain ganglion of the same level, many
preganglionic fibers go right through the ganglion and
ascend or descend through connecting processes
(rami) to other ganglia. Therefore,
the chain ganglia are found from the neck (superior cervical
ganglion) all the way down to the pelvis.
The chain ganglia supply specific structures in the head
and neck and in the thoracic, abdominal, and pelvic viscera, and
also supply blood vessels (vasomotor
fibers), arrector
pili muscles
(pilomotor fibers), and sweat glands
(sudomotor fibers) in the
periphery. These postganglionic
fibers leave the chain ganglia through the gray
rami
communicantes and travel with the spinal nerves to their
target structures, often hitchhiking along a blood vessel to
reach their final destination.

Some preganglionic
axons do not synapse in chain
ganglia at all. They pass through the ganglia, forming bundles
called splanchnic nerves,
and eventually synapse in collateral sympathetic ganglia
(prevertebral ganglia) that are
near the target organs. The postganglionic
axons leave these ganglia to
synapse on the target tissue directly. See Figure 1- 15 for a
diagram of sympathetic neurons. These synaptic structures are
not like the usual motor nerve terminals. They occur along the
length of the axon, as illustrated by Figure
1-16. The individual terminals are
called varicosities, and this kind of synapse is called a
terminal en passage because the axon does not end there.
These synapses are different from central synapse; they may have
very wide "synaptic clefts" so that the
neurotransmitter must diffuse over a much wider area. The
presynaptic ending does not always
sit in close proximity to the postsynaptic
site, as does the cholinergic nerve
ending at the NMJ or central
synapses.

Because the collateral ganglia are located near the organ
innervated, the cell bodies often are intermingled with nerve
terminals in this area. This combination of
preganglionic
axons and terminals, collateral ganglion cells, and
postganglionic
axons and terminals, is called a
plexus. A plexus may contain both sympathetic and
parasympathetic components. Therefore, the conglomeration of
neural elements found on the ventral surface of the aorta and
large blood vessels, and in or near many organs innervated, are
located in autonomic plexuses. For details of the anatomy of the
many peripheral plexuses, consult one of the major
neuroanatomy or gross anatomy
textbooks.
The spreading out of the sympathetics
from the relatively restricted
preganglionic cells to the widely distributed ganglia,
and the less specific nature of the synapses, or
neuroeffector junctions,
provide the anatomical basis underlying the basic principal that
the action of the sympathetic nervous system is widespread. In
addition, the adrenal medullary
chromaffin cells, which produces the hormones
epinephrine (80 per cent) and
norepinephrine (20 per cent) for release into the
blood, can be considered a component of the
SNS. The greater
splanchnic nerves, arising from
the thoracic chain ganglia (but not
synapsing in them), contain
preganglionic sympathetic axons
that synapse on chromaffin cells of
the adrenal medulla. Stimulation of these axons results in the
release of epinephrine and norepinephrine into the blood, which
carries these compounds to effector tissues, augmenting the
action of the sympathetic nervous system. These hormones of
adrenal derivation can interact with receptors directly, and
also can be taken up by the sympathetic postganglionic
noradrenergic nerve terminals, stored, and used subsequently for
release as a neurotransmitter. This is an example of a compound
with both hormonal and neurotransmitter roles. It also should be
noted that adrenal glucocorticoids, released by the action of
ACTH (adrenal corticotrophic hormone), a stress hormone from the
anterior pituitary, can enhance production of catecholamines in
the adrenal medullary chromaffin cells, further enhancing
general sympathetic arousal.
The peripheral distribution of sympathetic nerves, once they
leave the ganglia, usually follows blood vessels. For example,
the sympathetic supply to the head comes almost entirely from
the superior cervical ganglion, the rostral-most ganglion
of the sympathetic chain. Many of the postganglionic fibers
travel along the surface of the carotid artery and it branches
to reach their eventual terminations on smooth muscles
(pupillary dilator muscle) and glands (mucosal glands) of the
head. Some sympathetic fibers travel with nerves, but only
rarely is a nerve composed mainly of postganglionic sympathetic
fibers (the splenic nerve is the best example).
In general, the sympathetic nervous system can function as a
single entity to prepare the body to cope with stress,
particularly a dangerous or frightening situation. The pupils
dilate, skin and gut blood vessels constrict, muscle blood
vessels dilate, bronchioles dilate to allow passage of more air,
heart rate increases, and more blood is pumped with each beat.
Table 1 - 1 summarizes the actions of the sympathetic nervous
system on various tissues.

The postganglionic sympathetic fibers achieve their effects
on peripheral tissue by releasing the neurotransmitter
norepinephrine (except for sweat glands, innervated by ACh
fibers). For this reason, they are called noradrenergic
or adrenergic neurons. Many available drugs affect
these neurons. The preganglionic cells use ACh as their
neurotransmitter, as do the LMNs, and are called cholinergic
neurons. The receptors on the ganglion cells are different
from those on skeletal muscle cells, although they both respond
to nicotine and are considered to be nicotinic cholinergic
receptors. They respond to the same transmitter ACh, but they
respond differently to other drugs that are applied to them.
This is important pharmacologically because it allows the
manipulation of one kind of receptor without necessarily causing
the same effect on the other receptors. For example, a drug
might be given that will partially block cholinergic: receptors
on muscle, causing relaxation of that muscle, but that drug will
not block cholinergic: preganglionic fibers from synapsing with
ganglion cells of the autonomic nervous system. More details
will be supplied concerning the pharmacological manipulation of
the autonomic nervous system following the next section on the
parasympathetic nervous system.
Parasympathetic Nervous System
The action of the parasympathetic nervous system is
mostly homeostatic, allowing the maintenance and repair of the
body. This particularly is the case with the process of
digestion, which depends extensively on the parasympathetic
system. Sympathetic arousal virtually shuts digestion down.
Parasympathetic stimulation is necessary for gut contractility,
motility, and peristalsis, and secretion of digestive enzymes
and other gut secretory products.
Anatomically, the parasympathetics are similar to the
sympathetics in having a two-neuron chain, with preganglionic
and postganglionic neuronal elements- but there the resemblance
stops. The parasympathetic preganglionic neurons have their cell
bodies in two areas of the CNS. The first area, the cranial
portion, is in the brain stem. Four cranial nerve nuclei contain
parasympathetic preganglionic cells. These are: (1) the
Edinger-Westphal nucleus, the parasympathetic portion of the
oculomotor nucleus that sends fibers with cranial nerve III; (2)
the superior salivatory nucleus that sends fibers with
cranial nerve VII; (3) the inferior salivatory nucleus
that sends fibers with cranial nerve IX; and (4) the dorsal
motor (or efferent) nucleus of the vagus, whose fibers
contribute to cranial nerve X. Figure 1-17 depicts a schematic
view of the brain stem with the approximate locations of
preganglionic cell bodies of the parasympathetic nervous system.
The second area of preganglionic cell bodies is in the sacral
spinal cord. These cells are located in the intermediate gray
of levels S2 to S4, the same zone of gray matter that
contains some preganglionic sympathetics in the thoracolumbar
regions. Because of the two locations of preganglionic cells,
this parasympathetic portion of the autonomic system is often
referred to as the craniosacral system.

The postganglionic neurons have their cell bodies in ganglia
that are usually very close to, or actually part of, the organ
innervated. In other words, preganglionic fibers of the
parasympathetic nervous system are long, traveling to the organ
innervated, while sympathetic preganglionic fibers are short,
traveling to chain or collateral ganglia. As a result, the
postganglionic parasympathetic fibers are rather short in
comparison to the postganglionic sympathetic fibers that must
travel to the organ innervated from their position closer to the
spinal cord. In the head, there are specific ganglia associated
with specifically innervated structures. Most of the remaining
postganglionic cell bodies are located in plexuses near the
aorta and its branches or in the organs themselves (called
intramural ganglia). For example, the parasympathetic supply
to the gut is located (1) in a plexus of cells between the
longitudinal and circular smooth muscle layers of the gut wall (myenteric
plexus, or Auerbach's plexus); and (2) in a
submucosal plexus (Meissner's plexus). These particular
arrangements allow coordinated constriction of the gut in order
to pass its contents along. Table 1-2 gives the location of
preganglionic's, postganglionic's, tissues innervated, and
function of parasympathetic stimulation in that tissue.

Blood vessels are not supplied with parasympathetic fibers,
but stimulation of the parasympathetic nervous system does
affect the circulatory system by inhibiting the sympathetics.
The result is dilation of gut and skin blood vessels, and
dilation of the blood vessels involved in engorgement of
erectile tissues.
Preganglionic parasympathetic cells are cholinergic (use ACh
as a neurotransmitter) just like the preganglionic sympathetics;
the postganglionic cells are also cholinergic, unlike the
noradrenergic postganglionic sympathetics. But the cholinergic
receptors on effector tissue differ in their chemical and
pharmacological characteristics, and are stimulated by muscarine
(muscarinic receptors), not nicotine.
Sympathetics and parasympathetics can exert their actions in
one of two ways - they can cause primary effects by stimulating
the target tissue or one can act to inhibit the other. This
accounts for the effects of parasympathetics on blood vessels
even though they have no parasympathetic innervation. In this
case, parasympathetics inhibit sympathetic tone or constriction
and thereby cause dilation. In fact, both of these activities
may occur at once. In the gut, sympathetics stop digestive
processes partly by direct action and partly by inhibiting
parasympathetic action. Often the sympathetics and
parasympathetics oppose each other in action, but there are
systems in which they complement each other, such as erection
and ejaculation. In addition, during some behavioral states such
as chronic stress, both systems may be active. The sympathetics
may cause the release of catecholamines and generalized arousal,
while the parasympathetics increase gastric secretion,
contributing to the production of stress ulcers.
c. Autonomic Neurotransmission
It is essential to have a general understanding of the
actions of drugs on the autonomic nervous system, because
many drugs given to patients affect autonomics either directly
or indirectly. Terminology is a problem in discussing autonomic
neurotransmission, so the following distinctions should be made
before the details are given.
1. Adrenergic (or noradrenergic) neurons are cells that use
norepinephrine as a neurotransmitter.
2. Adrenergic receptors (adrenoceptors) are receptors
that recognize and respond to norepinephrine, epinephrine, and
dopamine, such as the sympathetically innervated effector
tissues.
3. Cholinergic neurons are cells that use ACh as a
neurotransmitter.
4. Cholinergic receptors are receptors that recognize and
respond to ACh, such as those on ganglion cells, on
parasympathetically innervated effector tissue, or on skeletal
muscles.
Even though all preganglionic autonomic axons, postganglionic
parasympathetic axons, and LMN axons use ACh as a
neurotransmitter to stimulate postsynaptic receptors, that
receptor react differently to other drugs. It is known that
nicotine will stimulate the cholinergic receptors normally
stimulated by ACh from preganglionic autonomics and from LMNs,
but not those normally stimulated by ACh from postganglionic
parasympathetics. These postganglionic parasympathetic receptors
are instead stimulated by muscarine and are called muscarinic
receptors. Receptors sensitive to nicotine are called nicotinic
receptors. This choice of designation is perhaps unfortunate
because all nicotinic receptors are not equal. While they
all respond to nicotine, they respond differently to still other
drugs. For example, ganglionic blockers block the nicotinic
receptors on ganglion cells normally stimulated by ACh, but not
the receptors at the NMJ, which are also nicotinic.
Adrenergic receptors are also of at least two different
kinds. These are designated alpha and beta-adrenergic
receptors. These types of receptors not only respond to
different drugs, but cause different effects on the postsynaptic
site. In general, alpha-receptors are excitatory except in the
gut, where they are inhibitory; beta-receptors are inhibitory
except in the heart, where they are excitatory. Beta-receptors
can be further subdivided into beta1 receptors
(Cardiac muscle, fat cells) and beta2 receptors
(bronchi, blood vessels, lymphocytes). Alpha-receptors also have
been subdivided into at least two classes, alpha1
(mainly postsynaptic) and alpha.2 (mainly
presynaptic). These subdivisions are not rigid but may vary from
one system to another.
The actions of many drugs take place on the receptors. Drugs
that block receptors are usually named for the kind of receptor
they block (cholinergic blockers, ganglionic blockers,
adrenergic blockers, beta-blockers, alpha-blockers). They are
also called antagonists. Two very common antagonists for
the cholinergic system are (1) the muscarinic blockers,
atropine and scopalarnine; and (2) the nicotinic
blocker, curare. Common antagonists for the adrenergic
receptors are (1) alpha-blockers, phentolamine and
phenoxybenzamine, and (2) the beta-blocker, propranolol.
Drugs that mimic the effects of neurotransmitters are called
mimetics (sympathomimetics, parasympathomimetics, and
cholinomimetics). They also are called agonists.
6. Response of Peripheral Nerves to Injury
Peripheral neurons can be damaged in a number of ways-
trauma, disease, toxic chemicals, and nutritional deficiencies-
resulting in a peripheral neuropathy. If the cell body is
killed, no regeneration of the neuron can occur. After birth,
peripheral neurons do not divide, and new neurons are not
usually formed. However, if the injury occurs to the axon, if
the damage is not too severe, and if the distal and proximal
ends of the neuron are still close together, reinnervation can
occur. The distal portion of the axon dies and is phagocytosed
by Schwann cells (Wallerian degeneration). Sprouts
extend from the proximal end of the damaged axons, grow into the
intact "tube" left by the distal basement membrane, and travel
to the target effector tissue, where reinnervation occurs. When
the whole neuron is killed, it is possible that nearby neurons
can sprout axonal processes and reinnervate the tissue.
Sympathetic postganglionic axons (noradrenergic) are
particularly able to sprout and reinnervate a denervated tissue.
Another kind of injury can occur to peripheral nerves. The
neuron is dependent on the integrity of its myelin sheath for
proper function. Demyelinating diseases can damage axons
secondarily. If the Schwann cells cannot recover and cannot
remyelinate the neuron, the neuron will first lose conduction
velocity and eventually the unmyelinated segment can die. This
problem can alter the function of sensory, motor, and autonomic
nerves. However, since only the preganglionic autonomic axons
are myelinated within the ANS, this problem is mainly restricted
to those components.
D. SPINAL CORD
1. Gross Anatomy
The spinal cord lies in the vertebral canal, is surrounded by
meninges, and is bathed in cerebrospinal fluid (CSF), as is the
rest of the central nervous system (CNS). The spinal cord is
divided into segments based on the spinal nerves
associated with each segment. There are 31 segments grouped into
four major regions. From rostral to caudal these divisions are:
(1) cervical spinal cord, with 8 segments; (2) thoracic spinal
cord, with 12 segments; (3) lumbar spinal cord, with 5 segments;
and (4) sacral spinal cord, with 5 segments, and a single
coccygeal segment usually grouped with the sacral spinal cord.
During development, the vertebral column grows more rapidly
than the spinal cord it encloses. Therefore, in the adult,
vertebral levels do not correspond with spinal segments, even
though they are often designated in the same way. For example,
the designation C7 may refer to a vertebral level, to a spinal
nerve, or to a segment of spinal cord. In this chapter we will
use such a designation for the spinal segment only and will
refer to the others more specifically as C7 vertebral level, or
C7 spinal nerve. For example, an injury to an adult patient at
the T8 vertebral level will injure the spinal cord at
approximately the T10 segment. The spinal nerves are derived
from cord segments of the same number. For instance, the T8
spinal nerve is derived from spinal cord segment T8 and must
travel caudally within the vertebral canal to the T8 vertebral
level (opposite T10 spinal cord segment) before it leaves the
canal. In general, the cervical segments are one segment
different from the cervical vertebral levels. (The C5 vertebral
level is approximately at the C6 spinal cord level.) The
thoracic segments are approximately two segments different (the
T6 vertebral level is approximately at the T8 spinal cord
level). The T11 and T12 vertebral bodies correspond to the five
lumbar spinal cord segments. The adult spinal cord ends at
approximately the lower Ll vertebral level (see Fig. 1- 13). The
tapering end of the spinal cord in this area, composed of sacral
spinal segments, is called the conus medullaris.

Caudal to the conus medullaris, the vertebral canal is filled
with spinal nerves traveling to their appropriate vertebral
levels of exit. This bundle of spinal roots in the vertebral
canal is called the cauda equina (or horse's tail). A
spinal tap done to remove a sample of CSF is done in this distal
lumbar vertebral region because entry of the needle will be
below the caudal end of the spinal cord and is unlikely to
damage the spinal roots. The spinal nerves consist of components
carrying both input and output. The input (sensory component)
enters the spinal cord mainly through the dorsal roots.
The output (motor and autonomic components) exits the spinal
cord through the ventral roots. The dorsal and ventral
roots unite for each segment to form the spinal root for
that segment. In actuality, the dorsal and ventral root for each
segment is made up of six or more rootlets.
The spinal cord consists of two types of tissue, gray
matter and white matter, as does the rest of the CNS.
The gray matter consists of cell bodies arranged into clusters
called nuclei (not to be confused with the nucleus of an
individual cell). The white matter consists of axonal processes,
appearing white because of the presence of myelin surrounding
the larger fibers. Clusters of fibers are arranged into
tracts. These tracts are variously called pathways, columns,
channels, funiculi, fasciculi, lemnisci, and so on, but they are
all axonal processes communicating with other cells at a
distance.
In the spinal cord the gray matter is arranged in a
butterfly, or "H," pattern in the center of the cord and can be
subdivided further into a dorsal horn, a region of
intermediate gray, and a ventral horn. In the spinal
cord, dorsal is used synonymously with posterior and ventral
with anterior. In thoracic and upper lumbar segments, a lateral
horn is present at the lateral edge of the intermediate gray.
The white matter is arranged into dorsal, lateral, and ventral
funiculi, anatomical zones of tracts subdivided by the dorsal
and ventral horns. The gray matter can be subdivided further
into 10 lamina, or layers, called lamina of Rexed (Fig.
1-18). In the dorsal horn, lamina I (marginal layer) is
associated with spinothalamic projections, laminae II and III
(substantia gelatinosa) are associated with slow pain
processing, and laminae IV and V (nucleus proprius) are
associated with the processing of both slow and fast pain. The
dorsal horn is separated from the dorsolateral sulcus by the
entrance zone of the dorsal root fibers, called Lissauer's
zone. In the intermediate gray, laminae VI, VII, and VIII
contain interneurons. In the ventral horn interneurons of
laminae VII and VIII are present along with clusters of LMNs,
which collectively are called lamina IX. Lamina X is the
commissural gray found around the central canal, and in its
dorsal portion contains some preganglionic autonomic cell
bodies.

The spinal cord contains major processing zones for sensory,
motor, and autonomic portions of the CNS. Somatic input and some
visceral input enter the spinal cord through the dorsal roots,
and motor and autonomic output leaves the spinal cord through
the ventral roots. In addition, local neuronal processing in the
dorsal, intermediate and ventral gray matter regulates reflex
activity in the spinal cord. Converging supraspinal influences
from the brain regulate the final outflow from motor and
preganglionic autonomic neurons. The spinal cord also serves as
a diverging channel for ascending sensory information, destined
for both unconscious proprioceptive responses and conscious
interpretation. These secondary sensory channels and components
are understood most easily by subdividing them into their
individual components, which include reflex channels,
cerebellar channels, and lemniscal channels. Refer to
Table 1-3 for a summary of these components.

The tracts listed in Table 1-3, forming the spinal cord white
matter, will be discussed under the heading Systemic
Neuroanatomy. Specific areas of cells in the gray matter will
also be discussed as necessary with their functional
descriptions.
2. Spinal Reflexes
a. Introduction
A spinal reflex is an appropriate motor response to a
sensory stimulus, not requiring supraspinal input or higher
processing. Such a reflex will occur even if supraspinal
connections are removed or destroyed because of injury or
disease. As long as sensory input and lower motor neuron (LMN)
output are intact, a spinal reflex can occur. In fact, a spinal
reflex may be hyperresponsive in a cord-injured patient (for
example, mass reflexes or spastic muscle stretch reflexes). If
LMNs are destroyed, as in polio, these reflexes cannot occur
because no motor response is possible. Destruction of the
sensory input is more difficult because it is often much more
diffuse, but if all sensory input is destroyed, the reflex
cannot occur. This can occasionally be seen in severe peripheral
neuropathies.
The simplest example of a spinal reflex is the
monosynaptic reflex. In this reflex, a sensory neuron
synapses directly on a LMN. This reflex can be considered a
holdover from the primitive two-neuron nervous system. It is
fast and effective but not very flexible. In higher animals,
upper motor neuronal control, especially through cortical
regulation, can over-ride some reflexes or use this circuitry
for performing complex movements. However, the supraspinal
control present in intact animals makes the study of such
reflexes difficult. In order to study spinal reflexes in
isolation from upper motor neuronal or supraspinal control,
experiments are sometimes done on animals with lesions that cut
off supraspinal input (such as spinal or decerebrate
preparations). These experiments show what happens locally,
either in individual segments or in the whole spinal cord, but
do not show how these reflexes are integrated into more complex
motor behavior. The following discussion will include only
spinal responses, but it should be remembered that upper motor
neurons (UMNs) are extremely important for keeping LMNs and
reflex pathways in a state of readiness for voluntary movements,
as well as for initiating those movements.
There are basically two kinds of spinal reflexes,
cutaneous (or exteroceptive) reflexes and muscle
reflexes. The cutaneous reflexes are polysynaptic,
while muscle reflexes may be polysynaptic (Golgi tendon organ
[GTO] reflexes, reciprocal inhibition reflexes, distant
responses to muscle stretch reflexes) or monosynaptic (the
muscle stretch reflex). The cutaneous reflexes are a motor
response to cutaneous stimulation. They also are called
withdrawal reflexes or flexor reflexes. The term
flexor reflex is actually a misnomer because the motor response
does not have to be flexion. The only requirement is that the
motor response must be appropriate to the cutaneous stimulus.
Most withdrawals are flexion movements, but an extensor muscle
may also carry out appropriate movements. The second kind of
spinal reflexes, the muscle reflexes, adjust the tone and
reactivity of muscles.
b. Cutaneous Reflexes
Cutaneous reflexes permit withdrawal from noxious or
nociceptive stimuli. The sensory input originates from receptors
in the skin and deeper tissue. Because these receptors are on
the exterior of the body rather than in the viscera, they
sometimes are referred to as exteroceptors and the resultant
cutaneous reflexes as exteroceptive reflexes. Exteroceptors are
responsive to heat, cold, touch, and pain. There are several
different morphological types of receptors, and it has been
suggested that each type may report a different kind of
stimulus. Unfortunately, the question of which receptor reports
which stimulus (or even whether a single receptor reports a
single modality) has not been answered fully and will not be
discussed further. Consult a major textbook for the many
receptor types described by anatomists, and bear in mind that
few absolute statements regarding modalities conveyed by these
receptors can be made at present.
Painful or noxious stimulation of appropriate receptors
causes the withdrawal (usually by flexion) of the entire limb,
and sometimes of the entire body. Figure 1-19 shows a schematic
of the simplest kind of polysynaptic reflex, with a receptor R,
a primary sensory neuron S, synapsing on an interneuron I 1,
which in turn synapses on LMN A. LMN A innervates a flexor
muscle, F1. Stimulation of the receptor causes an
action potential to fire in the primary sensory neuron. The
primary sensory neuron synapses on the interneuron I1,
exciting this neuron. The interneuron synapses on the LMN,
causing it to fire an action potential in turn. The LMN action
potential depolarizes its terminal at the motor end plate and
releases acetylcholine as its neurotransmitter, which crosses
the neuromuscular junction and causes the muscle to contract,
completing a cutaneous reflex.
The actual mechanism of the reflex is usually more
complex than the simple reflex just described. When a
finger is burned (a noxious cutaneous stimulus), the whole arm
withdraws, not just the finger, or local flexor. Many muscles
contract in a coordinated fashion to cause the withdrawal. This
is done through interneurons that control the degree to which
other LMNs will fire, and therefore the degree to which other
muscles will contract. Generally speaking, the stronger, the
stimulus, the more interneurons will be recruited, and the more
muscles will be involved in the reflex. Figure 1-20 illustrates
this principle schematically. This schematic is similar to
Figure 1-19, but to it has added an additional excitatory
interneuron, I2 (remember that excitatory neurons are
represented by white or undarkened cell bodies and inhibitory
neurons have black or darkened cell bodies). A second LMN, B;
and a second flexor muscle, F2, that represents a
synergistic muscle; one that works with the first muscle. In
this case, excitation of the receptor and the primary sensory
neuron causes interneuron I1 and subsequently LMN A
to fire and muscle F1 to contract; but it also causes
the interneuron I2 to fire, exciting LMN B, resulting
in the contraction of muscle F2. Adding more
interneurons increases the possibility of greater responses and
provides an appropriate response for a given stimulus. The whole
body does not have to withdraw; only the part actually in danger
will withdraw, but the withdrawal has to be both effective and
quick, and sometimes will involve a total body response.

Withdrawal reflexes affect more than just the muscles on the
side of the body that receives the stimulus. Muscles on the
opposite side of the body may respond as well, because of
activation through interneurons. This is particularly true of
withdrawal of the foot and leg, perhaps from stepping on a tack.
The foot that steps on the tack withdraws by flexion of that
leg, but in order to maintain balance, the other leg must extend
to provide a strong pillar to keep the body from falling over.
This kind of reflex is called a flexion-crossed extension
reflex.
The processing that goes on in the spinal cord is diagrammed
schematically in Figure 1-21. On the right side, Figure 1-21 is
the same as Figure 1-20. The left side represents the left side
of the spinal cord. Stimulation to receptor R will ultimately
cause flexion of muscles F1 an F2 just as
in Figure 1-20, but the primary sensory neuron also stimulates
excitatory interneurons 13 and 14 on the
left side of the spinal cord. These interneurons excite LMNs C
and D, which in turn cause the contraction of extensor muscle E1
and its synergistic muscle represented by E2. Any
further processing diagrammed schematically in this manner will
become too complex to follow, so the following simplification
will be made. Figure 1-22 represents the same system as Figure
1-21. It is understood that the primary sensory neuron excites
interneurons that in turn excite LMNs. The LMNs will be
designated FLX for those exciting flexor muscles and EXT for
those exciting extensor muscles. For simplicity, the muscles
have been left out of the diagram.


Not only are flexors on the side of the stimulus and
extensors on the side opposite the stimulus excited. In order
for them to have optimal effect, the extensors on the side of
the stimulus and the flexors on the opposite side from the
stimulus are inhibited so that they will not be working against
the withdrawal reflex. This process is diagrammed in Figure
1-23. The inhibition of antagonist muscle groups is mediated
through inhibitory interneurons (dark circle), and the process
is called reciprocal inhibition. If a stimulus is
presented on the right, as it is in the diagram, the LMNs for
flexor muscles on the right will be excited, while those for
extensors on the right will be inhibited. LMNs for extensors on
the left will be excited, while those for flexors on the left
will be inhibited.

Maintaining balance while withdrawing a whole leg may require
more than simply extending the other leg. Movement of the arms
may be needed as well, to offset the loss of balance. Therefore,
these reflexes can involve all four limbs and the trunk at once.
These reflexes are often referred to as long spinal reflexes,
but the movement of each limb is appropriate to withdrawal
from the noxious stimulus and maintenance of balance during the
movement, and will involve both flexion and extension.
The preceding discussion has considered what happens when one
noxious stimulus is presented alone. It is important to note
that when more than one such stimulus is presented, one stimulus
may have priority over the others, preventing appropriate
responses to the latter. Pain usually has precedence over other
reflexes. For example, if a scratch reflex is being elicited
from a dog, pinching the dog’s foot can stop it. The foot will
then be withdrawn. When the painful stimulus is stopped, the
scratch will resume.
c. Muscle Reflexes
Muscles have two specialized kinds of receptors: muscle
spindles and Golgi tendon organs (GTOs). These receptors are
responsible for reporting information about muscles to the
spinal cord for spinal reflexes and to special nuclei in the
spinal cord and medulla that relay the information to the
cerebellum (see the discussion of cerebellar channels). Muscle
spindles report static information concerning the length or
amount of stretch of individual muscle fibers, and dynamic
(phasic) information concerning the speed with which an active
muscle fiber is being stretched. The GTO reports the amount of
tension on a tendon from the passive stretch or contraction of
the muscle. This information is called proprioceptive
information and is necessary for two kinds of processing:
(1) in the spinal cord, it provides input to LMNs and
interneurons for local reflexes such as the muscle stretch
reflex; and (2) in the cerebellum, via synapses in the spinal
cord or medulla, it reports the state of the muscles so that the
cerebellum can coordinate the superimposition of voluntary
movements directed by the cortex, or adjustments in tone and
posture directed by brain stem UMNs.
d. Muscle Spindles
The muscle spindle is a sophisticated sensory receptor
that reports sensory information from muscles to the CNS and has
its own motor innervation through by which it can be adjusted by
the CNS. This mechanism assists the CNS by providing continuous
sensory feedback from the muscles.
(1) Anatomy of the Muscle Spindle. The muscle spindle is
made up of special types of muscle fibers called intrafusal
fibers, attached in parallel with the skeletal muscle
(extrafusal) fibers. It is attached at both ends to inelastic
collagen tissue associated with a skeletal muscle fiber. The
extrafusal fibers are responsible for generating the contractile
power of the muscle (Fig.1-24A). The muscle spindle is
surrounded by a capsule, which is attached at each end to the
connective tissue of the skeletal muscle fiber about which it is
reporting information. The spindle contains two types of
intrafusal fibers attached to the capsule on the inside,
chain fibers and bag fibers (Fig. 1-24B). These
fibers have an equatorial or middle region that contains
cell nuclei and a polar or end region that can contract
in response to motor input to increase tension on the equatorial
regions. The bag fiber has its nuclei arranged bag-like, in a
central cluster, and the chain fiber has its nuclei arranged
chainlike, in a row. Each muscle spindle usually has four to six
chain fibers and one to two bag fibers. Fibers that are
intermediate between the bag and chain fibers have been
described, but their function is not well understood at present.

(2) Innervation. The muscle spindle has both sensory and
motor innervation (Fig. 1-25). The sensory innervation consists
of group Ia fibers and group II fibers, which are sensitive to
the tension of the equatorial regions of the bag and chain
fibers. Group la endings wrap mainly around the
equatorial zone of the bag fibers. These Ia fibers are also
called primary endings, or annulospiral endings.
Group II endings innervate mainly the chain fibers. They
are also called secondary endings, or flower spray
endings. A stretch or tension on the equatorial
region of the group Ia and II fibers will cause them to fire
action potentials. The sensory input goes into the spinal cord,
as discussed earlier, and synapses on LMNs or their
interneurons, and on relay nuclei sending information to the
cerebellum.

The motor innervation is derived from two types of gamma
motor neurons (fusimotor neurons), gamma1 and
gamma2, to be distinguished from alpha motor
neurons (skeletomotor neurons). Gamma1 endings,
also called plate endings, innervate mainly the polar
ends of the bag fibers, and gamma2 endings,
also called trail endings, end mainly on the chain fiber,
near the polar region. Firing of these fusimotor neuron's
results in contraction of the polar region of the muscle
spindle, stretching or putting tensions on the equatorial
region. Stretching of the equatorial region causes the sensory
la and II fibers to fire. The resultant stimulation of
skeletomotor neurons in the anterior (ventral) horn of the
spinal cord causes the skeletal muscle fibers to contract.
Experimental stimulation of the fusimotor neurons causes spindle
fibers to contract, but adds negligible strength or power to the
contraction of the skeletal muscle without the stimulation of
skeletomotor neurons. A tightening of the muscle spindle causes
the Ia and II fibers to report specific kinds of sensory
information to the CNS.
(3) Function. Changes in skeletal muscle activity cause
changes in the muscle spindle. Passive stretch of the muscle by
tapping on a tendon, or experimental stretch of a muscle by
hanging a weight on it, will cause the muscle spindle to
stretch. As the spindle stretches, tension is put on the
equatorial regions, causing firing of la and II fibers.
Increased activity in the Ia fiber’s results in contraction of
the extrafusal muscle fibers, increasing the tension produced by
the skeletal muscle fibers. This shortening of the extrafusal
muscle fibers causes the spindle to slacken. Spindle slackening
decreases tension on the equatorial region and decreases the
firing of Ia and II fibers. In summary, the spindle reflex
responds to a stretch on the muscle by contracting the
extrafusal fibers, restoring the muscle to its original state
before the stretch. The spindle reflex therefore is a mechanism
for maintaining a muscle at a fixed state of contraction.
Relaxation of a muscle that has been contracted produces a
response of the spindle similar to stretching the muscle; the
sensory fibers increase their firing.
Gamma motor neurons act to modulate the length, and
consequently the tension, in the muscle spindle so that the
information reported to the CNS can be controlled. Contraction
of a muscle causes slackening of the spindle so that little or
no information goes into the CNS. Under these conditions, the
spindle would fail to report sensory information whenever the
muscle contracts. However, a resetting of spindle sensitivity is
achieved by the gamma motor neurons. These neurons, when
stimulated, contract the bag and chain fibers of the muscle
spindle by the gamma1 and gamma2 motor
fibers and cause the resumption of sensory information reporting
to the CNS. Figure 1-26 shows what happens to the firing of
group Ia and group II fibers during various activities. Type II
fiber's report only static information; that is, they report the
tension of the spindle, corresponding to the length of
the extrafusal muscle fiber. Group la fibers also report static
information to the CNS, but are even more important in reporting
dynamic information as well. In this capacity, they report the
speed with which the extrafusal muscle fibers are changing their
length (velocity).
In Figure 1-26A, the skeletal muscle is stretched passively
to a new length, which also stretches the muscle spindle. The
group II fibers respond to the new tension by increasing
their base rate of firing. The group Ia fibers also
respond with a new rate of firing, but during the time the
muscle fiber is changing its length there is a rapid burst of
activity that can be equated with velocity (or change in length
with respect to time) of muscle stretch. When stretching stops
and a new tension is reached, the group la fiber reports that
new static tension with a new firing rate. In Figure 1-26B, the
skeletal muscle is contracted, causing the muscle spindle to
slacken. Group II fiber’s decrease their firing to report the
new length. Group Ia fibers are silent during the period of
collapse, then resumes firing at a reduced rate corresponding to
the new extrafusal fiber length. It should be noted that when
contraction is initiated voluntarily or is adjusted by
supraspinal signals, those controlling signal’s are sent to both
the alpha and gamma motor neuron’s, thereby adjusting both the
extrafusal and intrafusal muscle fibers to maintain the muscle
spindle afferents in responsive range for the new extrafusal
length. In Figure 1-26C, the muscle tendon is tapped in order to
elicit a muscle stretch reflex. Group II fibers do not change
their firing rate because the tap is too fast for them to
respond. Group Ia fibers report a burst of firing during the
stretch part of the tap. It is this quick burst of Ia fiber
activity during the tap that causes the corresponding LMN to
which it projects to fire. This causes contraction of the
extrafusal fiber that was stretched originally, returning it to
its previous length.

The preceding discussion has not considered what happens when
the fusimotor neurons fire. Stimulation of these neurons
increases the responsiveness of the spindles. Stimulation of the
gamma1 or plate fibers, increases responsiveness to
both static and phasic events, while stimulation of gamma2,
or trail fibers, increases responsiveness to static events.
Mainly descending supraspinal channels, particularly those
channels that are influenced by cerebellar outflow, fires the
fusimotor neurons. On the other hand, stimulation of alpha motor
neurons does not influence directly the contractile elements of
the muscle spindle. These neurons cause the skeletal muscle
extrafusal fibers to contract and indirectly influence the
spindle through altered sensory activity caused by shortening of
the extrafusal muscle fibers. Figure 1-27 shows an Ia afferent
fiber synapsing directly on a LMN in the spinal cord. Ia
stimulation is the most powerful driving force for firing LMNs
and causing a muscle contraction or an increase in muscle
tension. This phenomenon is exploited clinically by
vibration, which can drive Ia afferents tonically, enhancing
the contraction of the associated muscle group, a process that
can be exploited therapeutically to excite a muscle group
antagonistic to a spastic muscle group, thereby reducing the
spasticity by reciprocal inhibition. It should be clear that the
fusimotor neurons, which can control the sensitivity or
responsiveness of the Ia afferent fibers, are critical to the
responsiveness of the alpha motor neurons and the control of
muscle tone.

Control of fusimotor neurons is from UMN systems that in part
keep the fusimotor neurons in check (inhibited). Damage of these
UMNs can cause a disinhibition of fusimotor neurons, increasing
their firing. The resultant increased stimulation causes the
muscle spindle to become more sensitive, which produces more
vigorous firing of Ia afferents to stretch, and finally results
in an increase in muscle tone brought about by increased LMN
firing and an exaggerated response to stretch reflexes owing to
the increased sensitivity of the muscle spindle. This increased
resistance to passive stretch is called spasticity.
When UMN control is present during normal tone and posture
and during normal voluntary movements, both skeletomotor and
fusimotor neurons are activated at the same time by the UMNs.
This alpha-gamma co-activation prevents the muscle
spindle from collapsing during the contraction of the skeletal
muscle, so that proprioceptive information is reported
continuously to the CNS. Therefore, both fusimotor and
skeletomotor neurons act in concert to achieve voluntary motor
actions and provide optimum sensory information to the CNS for
maximum evaluation of current motor activity and for regulation
of subsequent motor activity.
e. Golgi Tendon Organs
The Golgi tendon organ (GTO) is a receptor that is
connected in series with the muscle so that contraction of the
whole muscle increases tension on the tendon and excites the
GTO. Primary sensory afferents from the GTO called Ib fibers,
enter the spinal cord and synapse on interneurons associated
with LMNs, and in secondary sensory nuclei that relay
unconscious proprioceptive information concerning the state of
whole muscles to the cerebellum. The GTO is sensitive to
tension on the tendon and therefore is active during both
passive stretch and contraction. However, it is difficult to
elicit a normal GTO response during a clinical examination. The
Ib reflex associated with the GTO and the Ib afferent fiber is
an inhibitory reflex that prevents the muscle tendon from being
damaged due to excessive muscle contraction. Although the GTO is
extremely sensitive to tension on the tendon, and may help to
regulate inhibition necessary for alternating movements, no
single specific reflex for the Ib fiber can be elicited as
simply as can the Ia monosynaptic muscle stretch reflex.
However, Ib reflex activity can be demonstrated in a patient
with spasticity that has greatly increased tone in response to
passive stretch. Passive movement of the spastic limb will meet
with considerable resistance at first, followed by a collapse of
resistance as the passive movement is continued. The collapse is
called a clasp-knife reflex (named after the collapsing
of the blade in a pocket knife) and is thought to be the result
of Ib inhibition, preventing firing of overactive LMNs so that
the muscle will not be damaged because of excessive resistance
of the spastic muscle.
f. Muscle Reflex Activity
Each of the three types of afferent fibers just discussed
(Ia, II, and Ib) has an effect on several groups of muscles
through the LMNs supplying those muscles. LMNs supplying the
muscle from which the afferent fiber derives are called
homonymous LMNs. LMNs to the muscles that work with the
homonymous muscle are called synergist LMNs. LMNs to the
muscle groups that work against or opposite to the homonymous
muscle are called antagonist LMNs. Figure 1-28 shows
schematically how these reflexes affect their appropriate LMNs.
Ia afferents excite homonymous LMNs monosynaptically and
synergist LMNs polysynaptically through interneurons. Ia
afferents also inhibit antagonist muscle LMNs polysynaptically
through an inhibitory interneuron. Ib afferents work in the
opposite direction. They inhibit homonymous and synergist LMNs
disynaptically through inhibitory interneurons and excite
antagonist LMNs disynaptically. Group II reflexes doesn’t work
like Ia and Ib reflexes. The group II fibers are thought to
respond as a unit with a flexor bias. That is, they consistently
facilitate flexor LMNs and inhibit extensor muscle LMNs
polysynaptically. However, most research on group II responses
is conducted in non-primate animal models. The actual role of
group II fibers in humans is not understood adequately at
present, and definitive pronouncements about their role in
normal or neurologically damaged patients are not possible.

III. REGIONAL NEUROANATOMY
A. Major Subdivisions of the Nervous System
The mammalian nervous system is divided into a peripheral
nervous system (PNS), in contact with the outside world and the
internal world, and a central nervous system (CNS) that provides
integrated control of the periphery, interpretation of stimuli,
and generation of internal activities and thoughts. The contacts
between the outside world and the nervous system constitute the
sensory and motor components of the nervous system. The sensory
systems respond to stimuli from the external environment or the
internal milieu of the body while the motor system causes
skeletal muscles to contract, thus permitting movement and
behavior in response to the environment or as primary,
voluntarily initiated events. In addition, there is an autonomic
nervous system that has components in both the CNS and PNS. This
third functional component of the nervous system permits the
regulation of smooth muscle, cardiac muscle, secretory
(exocrine) glands, and other visceral organs (such as the liver
and immune organs), and operates as an internal visceral
regulatory control system.
The PNS has the following components: (1) primary sensory
cell bodies and axons, and associated receptors; (2) axons of
lower motor neurons (LMNs) and their neuromuscular junctions
(NMJ’s); (3) preganglionic axons, and ganglion cells and their
postganglionic axons of the autonomic nervous system; and (4)
the enteric nervous system, sometimes called the third division
of the autonomic nervous system, a collection of 100 million
neurons found in the gastrointestinal tract that aids the many
activities of that system.
The CNS can be subdivided into the following major regions,
based on the development of the brain:
- Spinal cord
- Rhombencephalon
- Myelencephalon-medulla
- Metencephalon-pons and cerebellum
- Mesencephalon-midbrain
- Prosencephalon (forebrain)
- Diencephalon (between brain)
- Thalamus
- Hypothalamus
- Subthalamus
- Epithalamus
- Telencephalon (end brain)
- Olfactory system
- Limbic system
- Basal ganglia
- Neocortex
The human brain possesses surface landmarks that can be used
to delineate these subdivisions (see Figs. 1-29 through 1-32).
The spinal cord is distinguished from the medulla by the
decussation (crossing) of the pyramids (corticospinal tract),
seen on the ventral surface of the caudal-most portion of the
medulla (Fig. 1-31). There are no clearly distinguishing
features on the dorsal surface of the caudal medulla at its
boundary with the spinal cord. The internal demarcation of the
spinal cord-medulla transition is gradual. Therefore, by
convention, an arbitrary division is made by a plane
perpendicular to the neuroaxis (long axis of the brain
stem) passing through the spinal cord just above (rostral to)
the first pair of cervical rootlets.


The demarcation of the rostral medulla from the caudal pons
is both clear and consistent. It consists of a plane through the
caudal boundary of the basis pontis of the ventral
surface of the brain stem, perpendicular to the neuroaxis (Fig.
1-31). This line of separation also marks the point where
cranial nerves VII (facial) and VIII (vestibulocochlear) emerge
from the brain stem at the medullopontocerebellar
(cerebellopontine) angle, and where the VI (abducens) nerve
emerges from the ventral surface.

The midbrain contains the cerebral peduncles on its
ventral surface. The caudal boundary of the midbrain is the end
of the basis pontis at its junction with the caudal-most
beginning of the cerebral peduncles. The caudal boundary of the
mammillary bodies in the hypothalamus delineates the
rostral boundary of the mesencephalon. The dorsal surface of the
midbrain contains two sets of small protrusions, or hillocks,
the inferior and superior colliculi (Fig. 1-32).
The colliculi are called the quadrigeminal bodies, which
make up the midbrain tectum.
The diencephalon is a direct rostral continuation of the
brain stem. The boundaries of the diencephalon include the
mammillary bodies at the caudal end, located at the base of the
brain, and the anterior commissure and lamina
terminalis, located at the rostral. end of the third
ventricle just above the optic chiasm (see Fig.
1-30). A plane passing perpendicular to the ventral surface of
the brain at the rostral boundary of the hypothalamus separates
the diencephalon caudally from the basal telencephalon
rostrally. In addition, surrounding the diencephalon is an outer
mantle of telencephalon containing limbic forebrain, basal
ganglia, and neocortical structures. In order to dissect
specific regions of the thalamus and hypothalamus, it is
necessary to remove or cut through an outer telencephalic shell
of structures. Further subdivision of the telencephalon is based
upon a functional parcellation of structures into the olfactory
system, limbic system, basal ganglia, and neocortex.
Each of the regions just noted contains specific areas,
tracts, and nuclei that will be considered in further detail.
The spinal cord has been discussed in a previous section as a
model for CNS organization. In the
following section the brain stem (medulla,
pons, midbrain, and cerebellum) and
forebrain (diencephalon and
telencephalon) will be discussed in a regional fashion. Even
though regional neuroanatomy is the main focus of this portion
of the chapter, the description still contains a strong systemic
orientation. With this approach, regional neuroanatomy makes
more sense functionally, rather than merely being a recounting
of innumerable anatomical structures.
A good atlas and Figure 1-29 through 1-32 should be referred
to continually as this section is read so that the structures
discussed can be visualized. Because the
PNS and the spinal cord already were described in the
last section, we will begin here with the brain stem.
B. Brain Stem
1. General Organization of the Brain Stem
The brain stem is made up of the medulla,
pons, midbrain, and cerebellum.
These regions are so closely related that they are best
considered as a functional unit. While some anatomists consider
the diencephalon to be part of the
brain stem, we do not; the diencephalon
is a highly specialized structure that will be considered
separately. The nuclei and tracts of the brain stem are
intermingled and appear scattered. However, they do follow
functional patterns in the medulla, pons,
and midbrain. These three major subdivisions contain six major
components that form the basis for regional anatomy for each
subdivision. There obviously is overlap, in some cases, of
certain components (such as the sensory, motor, and autonomic
cranial nerve nuclei).
a. Motor Systems
- Lower Motor Neurons. The cell bodies are
located in the brain stem and the
axon’s exit through cranial nerves to innervate
muscles of the head and neck.
- Upper Motor Neurons. The cell bodies are located
in the brain stem; the axons
descend to the LMNs and
associated interneurons,
which they control.
- Descending Motor Pathways. The pathways
(e.g.
corticospinal tract) consist of
axons of
UMN system’s that are
passing through the region on the way to
LMNs and associated
interneurons at lower
levels.
b. Autonomic Systems
- Parasympathetic Preganglionic
Cell Bodies.
The cell bodies are located in specific
nuclei in the brain stem and the
axons exit through cranial nerves III,
VII,
IX, and X to
terminate in parasympathetic ganglia near the cardiac
muscle, smooth muscles, secretory
glands, and viscera those ganglia supply (see Fig. 1-
17).
Autonomic Centers. These centers regulate major
visceral functions such as respiration, cardiac
function, blood pressure, and gastrointestinal
functions. These centers are sometimes viewed as complex
regulatory regions of the reticular formation and can
involve integrated sensory, motor, and autonomic
activities. The reticular formation will be discussed
later in this section.
Descending Autonomic Pathways. Cell bodies from
the hypothalamus, amygdala, and cerebral cortex, as well
as from the brainstem itself, sends axons that descend
through the brain stem to terminate in preganglionic
autonomic nuclei or associated regions, such as nucleus
solitarius.Additional descending pathways can involve
polysynaptic channels to the preganglionic neurons.
c. Sensory Systems
- Secondary Sensory Nuclei. These cell bodies
receive input from primary sensory axons and send
projections toward higher structures, particularly the
thalamic sensory projection nuclei. All primary sensory
cell bodies are found in ganglia associated with
peripheral or cranial nerves, except for the
mesencephalic nucleus of V, which is the only primary
sensory cell group within the CNS. Primary sensory
ganglion cells project to the secondary sensory nuclei
through the peripheral and cranial nerves, and
associated primary sensory tracts, such as the solitary
tract, the descending tract of V, or fasciculi gracilis
and cuneatus.
- Ascending Pathways and Relay Center. The
pathways are mainly ascending secondary sensory
(lemniscal) channels. The relay centers include tertiary
nuclei or nuclei associated with sensory processing, and
give rise to tertiary sensory channels.
d. Cerebellar Systems
(1) Cerebellar Cortex. The cerebellar cortex includes
three cell layers: molecular, Purkinje, and granular.
(2) The Medullary Zone. This region consists of white
matter deep to the cerebellar cortex.
(3) Deep Cerebellar Nuclei. These outflow nuclei are
located near the roof of the fourth ventricle.
(4) Peduncles. These structures are the input and output
axonal channels of the cerebellum, including the inferior,
middle, and superior cerebellar peduncles, that attach the
cerebellum to the brain stem. (5)Associated Cerebellar Input
Nuclei. The cell bodies are found in the brain stem (and
spinal cord, as discussed previously) and the axons project
through the peduncles to the cerebellum.
e. Reticular Formation
This general region, forming the core of the brain stem and
the most ancient supraspinal control systems, includes nuclei,
pathways, and centers that control visceral, motor, and sensory
functions necessary for life. The reticular formation includes a
medial two third (mainly motor), a lateral one third (mainly
sensory), the midline raphe, and scattered catecholamine
systems. It is responsible for maintaining consciousness,
maintaining general muscle tone and posture, processing noxious
stimuli, regulating major visceral functions, and providing a
host of interconnecting links that are reflex and integrative,
and allow quick and appropriate adjustments to disturbances in
the external or internal environment.
f. Cranial Nerve Nuclei
These nuclei include components of the sensory, motor,
and autonomic systems. This category directly overlaps with
categories 1, 2, and 3, and is best considered in these other
categories.
C. Medulla
1. Motor Systems
a. Lower Motor Neurons
Several motor cranial nerve nuclei are found in the medulla.
The hypoglossal nucleus (Nucleus XII) is found near the
midline and sends axons through the hypoglossal (XII) nerve to
innervate the muscles of the tongue.
The nucleus ambiguus is located in the ventrolateral
medulla and sends axons through the glossopharyngeal (IX), vagus
(X), and spinal accessory (XI) nerves to innervate
palatopharyngeal and laryngeal muscles and the esophagus.
The spinal accessory (XI) nucleus is located in the
ventral gray matter of the upper cervical spinal cord; it sends
axons through the XI nerve to the sternocleidomastoid and the
trapezius muscles. Although the LMNs are found in the spinal
cord, the axons travel with a cranial nerve.
b. Upper Motor Neurons
The gigantocellular reticular nucleus in the medial
reticular formation sends axons that run in the medullary
(lateral) reticulospinal tract. This tract is mainly
excitatory to flexor LMNs through interneurons and aids in the
general maintenance of tone.
The lateral vestibular nucleus sends axons that run in
the lateral vestibulospinal tract. This tract is mainly
excitatory to extensor motor neurons, with a few direct
connections and a predominance of indirect connections through
interneurons. It aids in the maintenance of antigravity tone,
particularly in response to vestibular stimulation.
The medial vestibular nucleus sends axons that run in
the medial vestibulospinal tract. This tract terminates
both directly and indirectly on cervical LMNs and regulates neck
movements in response to vestibular input, for maintenance of
head position.
Raphe nuclei of the medulla (obscurus, pallidus, and
magnus) send descending axon’s through scattered zones of
the medulla and through the lateral and ventral funiculus of the
spinal cord. These axons terminate in the ventral horn and aid
in the maintenance of tone, perhaps enhancing or reinforcing the
action of other neurotransmitters on LMNs (neuromodulatory
action). This descending bulbospinal pathway influences sensory
functions and is necessary for narcotic analgesia to occur, and
also influences preganglionic autonomic activity.
c. Descending Motor Pathways
Several pathways descend through the medulla on their way to
spinal cord interneurons and LMNs. The corticospinal tract (pyramidal
tract) arises in frontal and parietal lobes and descends
through the internal capsule, cerebral peduncles, and basis
pontis. Continuing its descent in the ventral medulla, 80 per
cent of the fibers decussate at the caudal-most midline region
of the medulla. The crossed portion continues into the spinal
cord as the lateral corticospinal tract. while the
uncrossed portion continues as the anterior corticospinal
tract and then mainly crosses into the contralateral ventral
horn through the anterior white commissure of the spinal cord.
The corticospinal tract regulates fine skilled hand and finger
movements, with a predominant influence on flexor LMNs.
The rubrospinal tract arises in the red nucleus of the
midbrain, crosses the midline in the ventral tegmental
decussation of the midbrain, descends through the
ventrolateral medulla, and has a predominant influence on flexor
LMNs.
The pontine reticulospinal tract arises in the pontine
reticular formation, descends through the ventral medulla, and
mainly influences extensor LMNs concerned with tone and posture.
The tectospinal tract arises from the superior
colliculus and to a lesser extent from the inferior colliculus,
crosses the midline in the dorsal tegmental decussation,
descends through the medial longitudinal fasciculus, and
terminates mainly in the cervical spinal cord. This tract
influences neck movements in response to visual and auditory
stimuli.
The noradrenergic bulbospinal tract arises in the
locus coeruleus and in noradrenergic nuclei of the brain stem
tegmentum, descends in the lateral and ventral regions of the
medulla, and influences general LMN tone in addition to
autonomic functions.
2. Autonomic Systems
a. Parasympathetic Preganglionic Cell Bodies
The dorsal motor nucleus of X and related cells in the
lateral reticular formation and commissure nucleus send
preganglionic parasympathetic fibers through the X nerve to
ganglia located near the visceral organs innervated. This system
supplies the heart lungs, and gastrointestinal viscera. Cell
bodies supplying the heart are found in the lateral reticular
formation around the nucleus ambiguus. Cell bodies supplying the
lungs and gastrointestinal viscera are found in the main nucleus
of the dorsal motor nucleus of X, the commissure nucleus of the
caudal medulla, and dorsal lamina X of Rexed of the first six
cervical spinal cord segments.
The inferior salivatory nucleus sends preganglionic
parasympathetic fibers through the IX nerve to the otic
ganglion. This ganglion supplies fibers to the parotid gland,
producing salivation.
b. Autonomic Centers
Numerous visceral centers have been described in regions of
the reticular formation of the medulla. These centers act
through the preganglionic autonomic cells and also influence
some LMNs. These regions include centers for blood pressure
regulation, heart rate and contractility, respiratory control,
and emetic responses.
c. Descending Autonomic Pathways
Processes from cell bodies in the hypothalamus
(paraventricular nucleus and several other zones), central
amygdaloid nucleus, and cerebral cortex (frontal, cingulate, and
insular) descend directly to the dorsal motor nucleus of X and
nucleus solitarius. Some of these cell groups send axons down to
the spinal cord to end on preganglionic neurons in the
intermediolateral cell column. Other systems descend indirectly
(anterior hypothalamus) through the dorsal longitudinal
fasciculus to the dorsal tegmental nucleus; and then to the
dorsal motor nucleus of X. In the lateral aspect of the medulla,
central sympathetic fibers polysynaptically descend from the
hypothalamus to the preganglionic sympathetic neurons in the
thoracolumbar areas of the spinal cord.
3. Sensory Systems
a. Secondary Sensory Nuclei
The nuclei gracilis and cuneatus are found in the medial
portion of the dorsal medulla at its caudal zone. These nuclei
receive input from dorsal root ganglion cells carrying epicratic
modalities (gracilis, T6 and below; cuneatus, above T6) via
fasciculi gracilis and cuneatus, and send crossed fibers through
a decussation in the caudal medulla to form the medial
lemniscus. The medial lemniscus ascends to the ventral
posterolateral (VPL) nucleus of the thalamus. The nuclei
gracilis and cuneatus also receive some information about
vibratory sensation, joint position, and cutaneous sensation
through projections from spinal cord neurons that travel in the
dorsolateral funiculus.
The nucleus of the solitary tract, located in the
dorsal medulla, receives cardiac and respiratory reflex
afferents, and taste fibers from the geniculate, petrosal, and
nodose ganglia, via nerves VII (facial), DC, and X,
respectively. The rostral portion of this nucleus, subserving
taste, gives rise to a crossed projection, the
solitariothalamic tract. This tract ascends to the
ventral posteromedial (VPM) nucleus of the thalamus, and also
sends projections to brain stem nuclei such as the parabrachial
complex; the caudal portion of nucleus solitarius. It processes
incoming information from sensory systems such as the carotid
sinus and carotid body, and regulates autonomic outflow from the
parasympathetic vagal complex and the sympathetic
intermediolateral cell column of the thoracolumbar spinal cord.
The descending (spinal) nucleus of V (trigeminal
nerve), located at the lateral margin of the medulla, receives
input from the trigeminal (gasserian or sernilunar) ganglion
cells carrying protopathic modalities such as pain and
temperature from the face and oral cavity. Some fibers carrying
epicratic sensation (touch) from the face, and fibers from the
pharynx and posterior 1/3 of the tongue (nerve IX for general
sensation) also terminate in this nucleus. This elongated
longitudinal nucleus sends crossed fibers into the ventral
trigeminothalamic tract (VTTT) which ascends toward the
ventral posteromedial (VPM) nucleus of the thalamus. Some fibers
from cells of this nucleus also terminate in reticular formation
and project toward nonspecific nuclei of the thalamus, as routes
for transmission of slow pain.
Vestibular nuclei (medial, lateral, and inferior) are
found in the medulla and continue into the pons (superior).
These nuclei receive vestibular input from Scarpa's ganglion via
the VIII nerve (vestibular part of the vestibulocochlear nerve).
This input carries information reporting angular acceleration
from the semicircular canals (movement) and linear acceleration
from the utricle and saccule (gravitation). The secondary
sensory afferents from the vestibular nuclei project to the
spinal cord (medial and lateral vestibulospinal tracts),
to the cerebellum (along with some ganglion cell projections,
through the medial portion of the inferior cerebellar peduncle,
the juxtarestiform body). They also project to the
reticular formation through local reflex channels, and to the
cranial nerve nuclei supplying extraocular muscles (III,
oculomotor, IV, trochlear, VI, abducens) via the medial
longitudinal fasciculus. These channels permit a coordinated
activation of extensor musculature of the body, neck
musculature, and extraocular musculature in response to
vestibular input.
b. Ascending Pathways and Relay Centers
Several ascending tracts arise in or pass through the
medulla. The medial lemniscus carries epicratic modalities from
the body. The spinothalamic tract carries protopathic
modalities, particularly fast pain, temperature sensation, and
light moving touch from the body, while the spinoreticular
tract carries slow pain from the body. The ventral
trigeminothalamic tract and its additional projections to
reticular formation carry protopathic modalities from the face,
oral cavity, anterior two-thirds of the tongue, and sinuses. The
solitariothalamic tract carries taste and visceral
sensory information. The medial longitudinal fasciculus
carries unconscious vestibular information to the extraocular
cranial nerve nuclei.
4. Cerebellar Systems
The cerebellar cortex, deep nuclei, and peduncles will be
considered separately in the section on the cerebellum. In the
medulla, several tracts and nuclei project to the cerebellum.
Spinocerebellar tracts carry unconscious proprioceptive
information to the cerebellum from the body. This information
includes Ia afferents from individual muscle fibers (dorsal
spinocerebellar tract from Clark's nucleus of the spinal
cord from T6 and below; cuneocerebellar tract from the
medullary lateral (accessory) cuneate nucleus for above
T6), and Ib afferents from whole muscles (ventral
spinocerebellar tract from spinal cord border cells
for T6 and below; rostral spinocerebellar tract from
spinal cord intermediate gray [mediobasal nucleus] for
T6). These tracts enter the cerebellum through the inferior
cerebellar peduncle, except for the ventral spinocerebellar
tract, which enters through the superior cerebellar peduncle.
For a schematic diagram of these cerebellar channels see Figure
1-34.

The inferior olivary nucleus is a large convoluted
nucleus in the ventrolateral medulla that sends climbing
fiber axons to the contralateral cerebellar cortex through
the inferior cerebellar peduncle. This nucleus is an important
motor feedback center and a spinal cord relay center for the
cerebellum.
The lateral reticular nucleus of the ventrolateral
medulla sends mossy fiber axons to the cerebellar cortex through
the inferior cerebellar peduncle. This nucleus conveys spinal
cord information from widely distributed sensory receptive
fields to the cerebellum.
The medullary vestibular nuclei and the vestibular (Scarpa's)
ganglion vestibulocerebellar projections through the
medial portion of the inferior cerebellar peduncle, the
juxtarestiform body.
Thus the inferior cerebellar peduncle is mainly a
channel conveying information from the spinal cord and
medulla to the cerebellum.
The inferior cerebellar peduncle carries some outflow from
the cerebellar cortex and deep nuclei. Some Purkinje cell
axons of the flocculonodular lobe and vermis project directly to
the ipsilateral laurel vestibular nucleus. Purkinje cell
axons from then arm travel to the fastigial nucleus which sends
fibers through die ICP to vestibular and reticular nuclei of
both sides of the brain stem.
5. Reticular Formation
The reticular formation is a collection of
longitudinally oriented large neurons with numerous collaterals,
giving rise to a tremendous amount of convergent and divergent
sensory, motor, and autonomic information. In the medulla, the
reticular formation contains several components. The lateral
third is a sensory zone, part of the ascending reticular
activating system, which receives widespread input from numerous
modalities and systems, This system aids in the maintenance of
consciousness and attention through projections to the adjacent
ascending portions which convey information to
nonspecific nuclei of the thalamus. The medial two thirds is a
motor zone that gives rise to the medullary reticulospinal
tract. This zone aids in the maintenance of tone and posture and
exerts a bias toward flexor LMNs.
The midline raphe nuclei and lateral
noradrenergic cell bodies give rise to descending serotonergic
and noradrenergic pathways. These tracts aid in the maintenance
of tone and posture and also play a major role in sensory and
autonomic functions. Autonomic centers regulating blood
pressure, cardiac function, respiratory function, and emetic
function are also found in the reticular formation.
6. Cranial Nerve Nuclei
Numerous cranial nerve nuclei are found in the medulla and
are discussed in the sections on motor, autonomic, and sensory
systems. These nuclei are associated with cranial nerve IX, X,
XI, and XII which leave or enter the medulla, and with cranial
nerve VIE, found at the medullopontine junction at the
cerebellopontine angle.
D. Pons
1. Motor Systems
a. Lower Motor Neurons
Three motor cranial nerve nuclei are found in the pons. The
facial nucleus (VII) is found in a lateral position in the
pontine tegmentum; it sends axons' dorsomedially to loop around
the abducens nucleus (genu of the facial nerve). These axons
then exit through the caudal pons ventrolaterally and innervate
the muscles of facial expression. The facial nucleus also
innervates the stapedius muscle and aids in dampening the
ossicles (stapes) in response to loud noises.
The abducens nucleus (VI) is found near the dorsal midline of
the rostral pons. Its axons run ventrally through the pons and
exit close to the ventral midline. This nucleus innervates the
lateral rectus muscle of the eye and is responsible for turning
the eye outward (lateral deviation).
The trigeminal motor nucleus (V) is found in the
lateral region of the mid pons and sends axons laterally and a
bit ventrally to exit through the mandibular division of the V
nerve. This nucleus innervates the muscles of mastication and
the tensor tympani muscle for additional dampening of the
ossicles (malleus) in response to loud noises.
b. Upper Motor Neurons
The caudal and rostral (also called oral) pontine
reticular nuclei are found in the medial two thirds of the
pontine reticular formation. These nuclei send predominantly
ipsilateral (uncrossed) axonal projections to the spinal cord,
where they terminate on interneurons associated with extensor
lower motor neurons (LMNs). This tract has a strong extensor
bias; it augments and reinforces the extensor bias of the
lateral vestibulospinal tract. The lateral vestibular nucleus
and its lateral vestibulospinal tract also are present in the
caudal pons. These were considered in the previous section on
the medulla.
The locus coeruleus is a pigmented nucleus (melanin)
located just beneath the lateral portion of the fourth ventricle
in the pons. This nucleus uses norepinephrine as its major
neurotransmitter, in addition to co-localized neuropeptides, and
sends noradrenergic axons to several structures, including the
cerebral cortex, hippocampal formation, cerebellar cortex, and
the spinal cord. The pathway to the spinal cord travels through
the ventral and lateral brain stem tegmentum and is augmented in
part by axons of noradrenergic cells found in the lateral and
dorsal medulla. These noradrenergic fibers aid in the
maintenance of tone and posture through interneurons and LMNs
and also contribute to the regulation of autonomic functions
through preganglionic autonomic neurons.
c. Descending Motor Pathways
Major motor pathways descend through the pons on their way to
interneurons and LMNs of the spinal cord. The corticospinal
tract descends through scattered fascicles in the basis pontis.
The rubrospinal tract and tectospinal tracts descend through the
tegmentum of the pons. These tracts also descend through the
medulla. They were discussed in greater detail in that section.
2. Autonomic Systems
a. Parasympathetic Preganglionic Cell Bodies
The superior salivatory nucleus is located in the
dorsomedial pons as a rostral continuation of the cell column of
the dorsal motor nucleus of X and the inferior salivatory
nucleus. This nucleus sends fibers through the facial nerve to
the pterygopaletine ganglion and the submandibular ganglion. The
pterygopaletine ganglion cells supply postganglionic
parasympathetic fibers to the lacrimal glands (tear production)
and to glands of the nasal mucosa. The submandibular ganglion
supplies postganglionic parasympathetic fibers to the
submandibular and sublingual salivary glands.
b. Autonomic Centers
A few additional autonomic centers are found in the pontine
reticular formation, rostral to the medullary centers. Some
respiratory functions are directed through pontine respiratory
centers. In addition, some "centers" for the control of blood
pressure has been described in the pons.
c. Descending Autonomic Pathways
Hypothalamic autonomic pathways and descending pathways from
limbic zones of the cerebral cortex and from the central
amygdaloid nucleus descend through the pontine tegmentum on
their way to sympathetic and parasympathetic preganglionic
neurons in the spinal cord and rhombencephalon, as discussed
earlier.
3. Sensory Systems
a. Secondary Sensory Nuclei
Sensory nuclei associated with the V and VIII nerves are
found in the pons. The dorsal and ventral cochlear
nuclei are located at the extreme lateral portion of the
dorsal zone of the caudal pons. They receive auditory input from
the cochlea through the spiral (auditory) ganglion and its
projections through the VIII nerve. The dorsal and ventral
cochlear nuclei send principally contralateral (crossed) fibers
through acoustic stria to innervate accessory nuclei or
to form ascending sensory channels. The upper part of the dorsal
cochlear nucleus gives rise to the dorsal acoustic stria;
the lower part of the dorsal nucleus and upper part of the
ventral cochlear nucleus give rise to the intermediate
acoustic stria, and the lower (anterior) part of the ventral
cochlear nucleus gives rise to the ventral acoustic stria,
also called the trapezoid body. These striae form the
lateral lemniscus, the major ascending auditory pathway.
Some fibers of the trapezoid body terminate in the superior
olivary nuclei. One portion of this nucleus (dorsal accessory
superior olivary nucleus) receives input onto dendrites from
both sides and assists in the localization of sound in space.
The superior olivary nuclei contribute fibers to both the
ipsilateral and contralateral lateral lemniscus. In addition,
some lateral lemniscus fibers terminate in accessory auditory
nuclei (nuclei of the lateral lemniscus, nuclei of the
trapezoid body). These nuclei also contribute both
ipsilateral and contralateral fibers to the lateral lemniscus.
The lateral lemniscus ascends to the nucleus of the inferior
colliculus. This entire auditory system is clearly a bilateral
system, accounting for the failure of a lesion above the level
of the pons to produce deafness with a discrete localization on
one side.
The main sensory nucleus of V is found just lateral to the
motor nucleus of V in the lateral portion of the mid-pons, and
receives input from trigeminal semilunar ganglion cells carrying
epicratic modalities from the face, oral cavity, and anterior
two thirds of the tongue via appropriate potions of the three
divisions (V1, ophthalmic; V2, maxillary;
V3, mandibular) of the trigeminal nerve. The dorsal
portion of this nucleus gives rise to the dorsal
trigeminothalamic tract (DTTT), which has been reported to
travel either ipsilaterally or contralaterally to the ventral
posteromedial (VPM) nucleus of the thalamus. It is not yet clear
how this projection system is organized, although the face is
thought to have epicritic representation onto the lateral
portion of the contralateral postcentral gyrus. Resolution of
this question awaits further tracing studies in primates. This
system carries fine discriminative modalities of the face for
conscious interpretation. Some cells of the main sensory nucleus
of V send crossed projections into the VTTT.
The descending nucleus of V also is found partially in pons
and has been discussed in the section on the medulla, where the
major portion of this nucleus is found. This nucleus gives rise
to the ventral trigeminothalamic tract (VTTT), which
carries mainly protopathic: modalities from the face toward
nucleus VPM of the thalamus. Some of the fibers of this system
reach nucleus VPM ("fast" pain and temperature sensation) while
other fibers ("slow" pain) end in the lateral reticular
formation.
The superior vestibular nucleus is located in the
pons. It contributes to the same extraocular, reticular
formation, and cerebellar channels as the other medullary
vestibular nuclei (inferior, lateral, medial). These channels
are discussed in further detail in the section on the medulla.
b. Ascending Pathways and Relay Centers
Several sensory tracts ascend through the pons. The medial
lemniscus carries epicritic modalities from the body. The
spinothalamic tract carries protopathic modalities, particularly
fast pain, from the body, while the spinoreticular tract carries
slow pain from the body. The ventral trigeminothalamic tract
carries mainly protopathic modalities from the face, oral
cavity, anterior two thirds of the tongue, and sinuses. The
dorsal trigeminothalamic tract carries epicritic modalities from
the same regions. The solitariothalamic tract carries taste and
visceral sensory information. The lateral lemniscus carries
auditory information. The medial longitudinal fasciculus carries
unconscious vestibular information to the extraocular cranial
nerve nuclei.
4. Cerebellar Systems
The basis pontis contains clusters of neurons located
in pontine nuclei. These nuclei act as a
cerebral-cerebellar relay channel. The pontine nuclei receive
input from all regions of the cerebral cortex and send axonal
projections to the cortex of the contralateral cerebellar
hemispheres in the form of mossy fibers. These pontocerebellar
fibers enter the cerebellum through their own peduncle, the
middle cerebellar peduncle. This relay pathway coordinates
voluntary motor activity, apparently initiated by the cortex,
with tone and position of the muscles at any given moment. This
relay pathway is concerned particularly with fine coordinated
movements.
The pons also contains passing fibers of the ventral
spinocerebellar tract (VSCT), which enters the cerebellum
through the superior cerebellar peduncle, and
trigeminocerebellar fibers, which enter the cerebellum through
both the superior and inferior cerebellar peduncles.
5. Reticular Formation
The pontine reticular formation contains the same
motor (medial two thirds) and sensory (lateral third) divisions
as the medullary reticular formation. The motor division aids in
the maintenance of tone and posture, and the sensory division
aids in the maintenance of attention and consciousness.
In addition, ascending monoamine pathways arise from
reticular formation nuclei of the pons. The locus coeruleus
sends ascending noradrenergic fibers that join other ascending
fibers from the lateral and dorsal medulla, and distribute to
the hypothalamus, thalamus, limbic forebrain, and cerebral
cortex through the brain stem tegmentum and the medial forebrain
bundle. This system participates in the regulation of
neuroendocrine functions and visceral functions (feeding,
drinking, regulation, reproductive behavior, autonomic
regulation) of the hypothalamus, emotional or affective
behavior, and cognitive and intellectual functions. Dysfunction
of this noradrenergic system has been implicated in depressive
illness. The dorsal raphe nucleus and central superior nucleus
send ascending serotonergic axons to the hypothalamus, thalamus,
limbic: forebrain, basal ganglia, and cerebral cortex through
the brain stem tegmentum and the medial forebrain bundle. This
ascending serotonergic system closely overlaps the ascending
noradrenergic: system. The serotonergic system has been
implicated in neuroendocrine and visceral hypothalamic function,
emotional behavior, and cognitive functions. These noradrenergic
and serotonergic pathways and their terminals are the major
sites of action of the drugs used to treat depressive and other
affective disorders.
6. Cranial Nerve Nuclei
Numerous cranial nerve nuclei are found in the pons, and they
are discussed in the sections on motor, autonomic, and sensory
systems. These nuclei are associated with cranial nerves VII and
VIII at the cerebellopontine angle and with cranial nerves V and
VI of the pons.
E. Midbrain
1. Motor Systems
a. Lower Motor Neurons
Two motor cranial nerve nuclei of the extraocular system are
found in the midbrain. The trochlear nucleus (IV) is found near
the midline of the caudal midbrain and innervates the superior
oblique muscle of the contralateral side. The fibers of the
trochlear nerve cross before exiting the brain stem. The IV
nerve is the only cranial nerve to exit the brain stem from its
dorsal surface. The superior oblique muscle depresses the eye
(moves the eye downward) when it is turned inward. The
oculomotor nucleus (III) is found near the midline in the
central gray just rostral to the IV nucleus. It innervates the
ipsilateral inferior oblique muscle and the medial, superior,
and inferior rectus muscles. The inferior oblique muscle
elevates the eye when it is turned inward. The inferior rectus
muscle depresses the eye when it is turned outward. The medial
rectus moves the eye medially, while the superior rectus
elevates the eye, particularly when it is turned outward. The
oculomotor and trochlear nuclei work with the abducens nucleus
to coordinate the six extraocular muscles of each eye for
coordinated conjugate movements of the eyes.
b. Upper Motor Neurons
The red nucleus is a large cell group found in the
medial portion of the ventral midbrain tegmentum. This nucleus
sends fibers that cross in the ventral tegmental decussation at
the level of the red nucleus and descend as the rubrospinal
tract, This tract descends in the lateral brain stem
tegmentum and the lateral funiculus of the spinal cord, and
terminates at all levels of the spinal cord. The rubrospinal
tract has a flexor bias and terminates mainly on interneurons.
It aids the corticospinal tract in overcoming antigravity tone
and in achieving skilled flexor movements.
The superior colliculus, and to a lesser extent the
inferior colliculus, send descending fibers across the midline
of the central gray of the midbrain in the dorsal tegmental
decussation, to descend as the tectospinal tract.
This tract terminates in the cervical spinal cord on
interneurons related to LMNs responsible for neck movements. The
tectospinal tract conveys visual stimuli and, to a lesser
extent, auditory stimuli, to elicit reflex movement of the head
and neck in response to these stimuli.
c. Descending Motor Pathways and Other Motor Structures
Cortical efferent fibers descend through the midbrain on
their way to lower brain stem and spinal cord structures. These
cortical fibers are respectively called corticobulbar and
corticospinal tracts. The corticospinal and corticobulbar
tracts descend through the middle three fifths of the cerebral
peduncles on the ventral surface of the midbrain.
The substantia nigra, a dopamine-containing nucleus in
the ventral midbrain tegmentum, just above the cerebral
peduncle, is a motor structure mainly associated with the basal
ganglia. The substantia nigra has reciprocal connections with
the caudate nucleus and putamen and helps to regulate the motor
activities of these structures. The basal ganglia enhance wanted
movements and suppress unwanted movements, working in concert
with the cerebral cortex. The importance of the substantia nigra
in motor functions has been underscored by the finding of
degeneration and depletion of dopamine neurons in this structure
in Parkinson's disease, a motor disorder characterized by
a resting tremor, muscular rigidity, and an inability to
initiate voluntary movements (bradykinesia).
2. Autonomic Systems
a. Parasympathetic Preganglionic Cell Bodies
The nucleus of Edinger-Westphal is found in the
midline of the central gray in the rostral midbrain, as a
rostral component of the oculomotor complex. The nucleus of
Edinger-Westphal sends axons ventrally, where they exit from the
interpeduncular fossa at the ventral surface of the midbrain in
the III nerve. These preganglionic parasympathetic fibers
terminate in the ipsilateral ciliary ganglion. The ciliary
ganglion supplies postganglionic fibers to the pupillary
constrictor muscle and the ciliary muscle. Activation of these
fibers produces pupillary constriction and accommodation to near
vision, respectively.
b. Descending Pathways.
Pathways descending from the hypothalamus and higher levels
to preganglionic neurons of the parasympathetic and sympathetic
nervous systems traverse the midbrain as well as the pons and
medulla. These systems were discussed in the section on the
medulla.
3. Sensory Systems
a. Sensory Nuclei
The midbrain colliculi are major visual (superior colliculus)
and auditory (inferior colliculus) relay centers. The superior
colliculus receives visual input from the optic (II) nerve, and
gives rise to both ascending and descending channels. The
ascending channel projects to the pulvinar of the thalamus,
which in turn conveys the visual information to associative
visual cortex (area 18, 19) of the occipital lobe. The
descending channels travel to the spinal cord via the
tectospinal tract and to the cerebellum via tectocerebellar
projections. Some zones of the superior colliculus also are
involved in some pain processing via input from spinoreticular
projections. The inferior colliculus; sends auditory information
to the medial geniculate body (MGB) of the thalamus via the
brachium of the inferior colliculus. The MGB in turn projects to
the auditory cortex of the temporal lobe.
The mesencephalic nucleus of V is a cluster of cells
scattered throughout the mesencephalon at the lateral edge of
the periaqueductal gray. Some neurons also are found in the
rostral pons just lateral to the lateral portion of the rostral
fourth ventricle. These neurons are the only primary sensory
cell bodies found within the CNS. Their peripheral processes are
Ia afferent fibers that innervate muscle spindles in masticatory
and extraocular muscles. The primary sensory axons enter the CNS
through the three divisions of the trigeminal nerve and then
travel in the tract of the mesencephalic nucleus of V.
This unconscious muscle spindle information is then conveyed to
other central structures, such as the motor nucleus of V,
forming the basis for the jaw jerk monosynaptic: reflex.
The periaqueductal gray of the midbrain is involved in
sensory processing of protopathic modalities. The periaqueductal
gray receives input from the reticular formation through
polysynaptic spinoreticular channels. In addition, very high
levels of endogenous opioid peptides, the enkephalins (cell
bodies) and the endorphins (nerve terminals from hypothalamic
cells) are found in the periaqueductal gray, further suggesting
a role for this structure in pain processing and analgesia.
Stimulation of specific portions of the periaqueductal gray with
electrical current can produce long-fasting analgesia, perhaps
through the enhanced activity of the opioid systems in that
area.
b. Ascending Pathways
The ascending pathways in the midbrain include those tracts
that ascend through the pons; they are summarized in the section
on the pons. In addition, tectal sensory pathways are found. The
brachium of the inferior colliculus carries auditory
information from the inferior colliculus of the MGB. The
tectopulvinar fibers carry visual information from the
superior colliculus to the pulvinar of the thalamus.
4. Cerebellar Systems
The superior cerebellar peduncle (SCP) connects the
cerebellum with the midbrain. This fiber bundle is mainly an
outflow system for the cerebellum but also conveys some input to
the cerebellum. The input comes from the ventral spinocerebellar
tract and some trigeminocerebellar fibers. The output comes from
the deep nuclei, which are in turn regulated by Purkinje cells
in the cerebellar cortex and by collaterals of secondary sensory
systems projecting to the cerebellum. Purkinje cells in the
paravermal region of the cerebellum project to the globose
and emboliform nuclei, which in turn project through the
SCP to the red nucleus and to a lesser extent to the
ventrolateral (VL) nucleus of the thalamus. Purkinje cells in
the lateral cerebellar hemispheres project to the dentate
nucleus, which in rum projects through the SCP to the
ventrolateral (VL) nucleus of the thalamus and to a lesser
extent to the rostral third of the red nucleus.
These projections from globose, emboliform, and dentate
nuclei cross the midline in the middle of the caudal midbrain
tegmentum through the decussation of the SCP. In
addition, these deep cerebellar nuclei also project fibers to
the reticular formation. The outflow from the deep cerebellar
nuclei permits the cerebellum to regulate motor activity through
the control of UMN systems, such as the motor cerebral cortex
(through the ventrolateral nucleus of the thalamus), the red
nucleus, and the brain stem reticular formation.
5. Reticular Formation
The midbrain reticular formation conveys axons of the
ascending noradrenergic and serotonergic pathways to the
forebrain structures, previously described in the section on the
pons. In addition, an ascending mesolimbic: and mesocortical
dopamine pathway arises from the ventral tegmental area
found in the midline of the midbrain surrounding and above the
interpeduncular nucleus. This dopamine pathway ascends to
nucleus accumbens and the olfactory tubercle (mesolimbic:
pathway to limbic forebrain structures), and to cerebral cortex,
particularly the frontal and cingulate cortex (mesocortical
pathway). This latter pathway has been implicated in emotional
and cognitive behavior, some investigators believe that
dysfunction of this dopaminergic system and its receptors on
target neurons characterizes schizophrenia, since the
anti-schizophrenic drugs, the phenothiazines, mainly alter this
system. This hypothesis awaits further substantiation.
Several midbrain nuclei that are intimately associated with
the hypothalamus and limbic forebrain structures have been
described. These midbrain nuclei (and some pontine components)
collectively are called the limbic midbrain area of
Nauta; they include the interpeduncular nucleus, the
ventrolateral periaqueductal gray, the dorsal raphe nucleus, the
central superior nucleus, and the dorsal and ventral tegmental
nuclei. These nuclei have reciprocal connections with the
hypothalamus (mainly the lateral portion) and in turn with the
limbic forebrain structures or area (LFA). A
schematic of these relationships is found in Figure 1-33. These
connections permit an integration of both midbrain and forebrain
limbic: structures through the hypothalamus.
Several midbrain structures are also concerned with
processing of pain. These regions include the lateral third of
the reticular formation, the central (periaqueductal) gray, and
part of the tectum, or colliculi. These structures receive input
from the polysynaptic spinoreticular system for protopathic
modalities and help to integrate the extremely complex and
diverse perception of pain. The periaqueductal gray contains
high levels of the newly discovered opioid peptides, the
enkephalins and B-endorphin. The enkephalins are found in small
neurons in this structure, while the B-endorphin is found in
nerve terminals whose cell bodies are found in the
periarcuate region of the ventrobasal hypothalamus.
These endogenous narcotic systems have a predilection for
pain-processing areas and may mediate analgesic effects of
chronic pain or pain associated with highly stressful, life
threatening circumstances. In addition, the lateral third of the
midbrain reticular formation is important in the maintenance of
attention and consciousness through the ascending reticular
activating system. Destruction of this system results in an
irreversible comatose state.

6. Cranial Nerve Nuclei
Several cranial nerve nuclei are found in the midbrain and
are discussed in the sections on motor, autonomic, and sensory
systems. These nuclei are associated with cranial nerves III and
IV of the midbrain, and to a lesser extend with cranial nerve V
of the mid-pons.
F. Cerebellum
The cerebellum is responsible for modulating coordinated and
smoothly integrated motor behavior. The major sensory input to
the cerebellum consists of: (1) unconscious proprioceptive
information channeled through the spinal cord via the four
spinocerebellar tracts; (2) vestibular information from the
vestibular nuclei and directly from Scarpa's ganglion through
the vestibular nerve; and (3) reticular formation projections
from prominent medullary reticular nuclei and some pontine
reticular nuclei. These inputs inform the cerebellum of the
position and state of contraction of the musculature and the
tension on the tendons throughout the body, the position of the
head in space, and the general activity of total-body sensation
from the reticular formation, respectively. They enter the
cerebellum through the inferior cerebellar peduncle,
except for the ventral spinothalamic tract, which enters through
the superior cerebellar peduncle. In addition, trigeminal
information (trigeminocerebellar fibers) enters the cerebellum
through the inferior and superior cerebellar peduncle and visual
and auditory information (tectocerebellar fibers) enters the
cerebellum mainly through the superior peduncle. Information
from the cerebral cortex also enters the cerebellum, synapsing
first in the pontine nuclei, which in turn send axons into the
contralateral cerebellar cortex through the middle cerebellar
peduncle. This corticopontocerebellar input informs the
cerebellum of movements that have been initiated through the
descending supraspinal systems such as the corticospinal and
corticobulbar tracts. The cerebellum can then coordinate and
interpret these planned movements and integrate them with
movements already in progress, whose feedback channels relay
back to the cerebellum through sensory-cerebellar input systems.
It should be noted that each side of the cerebellum receives
information from the ipsilateral side of the body. This is the
opposite of the cerebral cortex, which receives sensory input
from the contralateral side of the body.
The input to the cerebellum distributes to specific layers of
the cerebellar cortex (molecular, Purkinje, and granular cell
layers) in the form of climbing fibers (from the inferior
olivary nucleus), direct noradrenergic coeruleocerebellar fibers
(from the locus coeruleus), and mossy fibers (from all other
input nuclei). The climbing fibers synapse on the dendrites of
the Purkinje cell’s, the main output neurons of the cerebellum,
in a manner comparable to a vine adhering to the branches of a
tree. The mossy fiber terminate on granular cells of the
cerebellum which in turn project parallel fibers into the
molecular layer to synapse consecutively on the dendrites of
many Purkinje cells, whose dendritic trees are arranged
perpendicular to the parallel fibers. These parallel fibers pass
through the orderly parallel plane arrangement of the Purkinje
cell dendritic trees in a manner similar to telephone wires
running across hundreds of telephone poles, all arranged in a
straight row. In addition, complex local neurons (basket,
stellate, and Golgi II cells) modulate the cerebellar input
and processing to achieve a single coordinated and integrated
output through the Purkinje cells. The basket cells in the
molecular layer mainly inhibit Purkinje cell bodies, the
stellate cells in the molecular layer mainly inhibit Purkinje
cell dendrites, and Golgi cells in the granular layer mainly
inhibit mossy fiber input to granular cells. The output from the
cerebellar cortex arises solely from the Purkinje cells and
projects to the four deep cerebellar nuclei (fastigial,
globose, emboliform, and dentate nuclei) and to the lateral
vestibular nucleus (thought by some to be a displaced deep
cerebellar nucleus). These nuclei also receive collaterals from
the mossy fibers, the climbing fibers, and the noradrenergic
coeruleocerebellar fibers; the cerebellar cortical inputs to
these deep nuclei may function mainly to modulate this
connection from the input fibers to the deep nuclei. The
projections of the deep nuclei exit the cerebellum mainly
through the superior cerebellar peduncle and the medial portion
of the inferior cerebellar peduncle (juxtarestiform body). The
cerebellar outflow from the deep nuclei provides control over
UMN systems such as the corticospinal, rubrospinal,
vestibulospinal, and reticulospinal tracts. The cerebellar
outflow does not regulate LMNs directly; it influences these
neurons only through the UMN pathway.
The cerebellar cortex is thrown into a series of
convolutions, with gyri and sulci. The gyri are called folia
of the cerebellum. Grossly, the cerebellar cortex consists
of three longitudinal zones: (1) the vermis, in the midline; (2)
the paravermis, on either side of the vermis; and (3) the
lateral hemispheres, accounting for the bulk of the
cerebellar cortex in primates.
The vermal Purkinje cells project mainly to the fastigial
nucleus, which in turn regulates reticulospinal and
vestibulospinal systems through projections that travel in the
medial ICP. Some Purkinje cell axons project directly to the
lateral vestibular nucleus. The paravermal Purkinje cells
project mainly to the globose and emboliform nuclei,
which in turn regulate the rubrospinal system. The lateral
hemispheric Purkinje cells project mainly to the dentate
nucleus, which in turn regulates the corticospinal system
through the ventrolateral nucleus of the thalamus and its motor
cortical connections. The outflow of the globose, emboliform,
and dentate nuclei travels contralaterally to these target
structures through the SCP
An older system of anatomical description divides the
cerebellum into anterior, posterior, and flocculonodular lobes.
The flocculonodular lobes are phylogenetically the oldest part
of the cerebellum and evolved mainly to aid vestibular
processing. In general, the paravermis and hemispheres of the
anterior and posterior lobes mediate coordination of movements
of the extremities. The lateral hemispheres are
particularly important for the coordination of complex hand and
finger movements. It is therefore no surprise that the
cerebellar hemispheres increase in size and importance as the
motor portions of the cerebral cortex increase in size and
importance throughout phylogeny. Control of trunk musculature
and vestibular responses are mediated through the vermis and the
flocculonodular lobe.
The cerebellum performs several vital tasks. During normal
posture, the cerebellum must aid in the coordination of trunk
and proximal limb- muscles to permit smooth tone and posture, a
stable upright position of the body, and error correction for
minor shifts in posture. The cerebellum must also smooth and
coordinate complex movements of the distal extremities, must
carry out sophisticated feedback control of dexterous motor
activity, and must adjust moment-to-moment motor movements
through sensory feedback. The cerebellum must be recruited to
achieve control of UMN systems through the initiation of
specific neuronal cerebellar "subroutines" before skilled motor
acts can be learned and perfected. These numerous tasks account
for the need of the multimodal sensory input and cortical input
through the pontine nuclei
G. A Summary of the Cranial Nerves, Cranial Nerve
Nuclei, and Their Associated Ganglia
a. Cranial Nerves
The cranial nerves contain only three major functional
components: sensory (S), motor (M), and autonomic
parasympathetic (A). While other classification systems
subdivide these components into numerous categories based upon
developmental considerations, they do little to enhance the
functional understanding of the cranial nerves. Rather, they
obscure a rather simple system with an archaic and confusing
exercise in terminology. A summary is given in Table 1-4, based
on a straightforward functional classification.
To summarize further, the cranial nerves are mainly
sensory, mainly motor, or mixed nerves:
Sensory nerves: I, II, VIII
Motor nerves: III, IV, VI, XI, and XII
Mixed sensory and motor nerves: V, VII, IX, and X
Nerves carrying preganglionic parasympathetic fibers:
III, VII, IX, and X
b. Motor Nuclei (Brain Stem Lower Motor Neurons)
For a summary of cranial nerve motor nuclei, see Table 1-5.

c. Sensory Nuclei
A summary of the cranial nerve sensory nuclei is given in
Table 1-6. Nuclei associated with the olfactory and optic nerves
are not included in this summary because nerves I and II are CNS
tracts and not true peripheral nerves, as are cranial nerves III
through XII.

d. Cranial Preganglionic Parasympathetic Nuclei
Table 1-7 contains a summary of the cranial preganglionic
parasympathetic nuclei.

H. Forebrain (Prosencephalon)
1. Diencephalon
The diencephalon consists of two major parts, the thalamus
and the hypothalamus. In addition, the epithalamus
and subthalamus also are classified as part of the
diencephalon. The subthalamus is most properly an accessory
nucleus associated with the basal ganglia, while the
epithalamus, particularly the habenula, is associated
with limbic system connections. These two minor components of
the diencephalon will not be considered further in this section.
a. Thalamus
The thalamus is the major sensory relay station to the
cerebral cortex, acting as the gateway to neocortex for
ascending lemniscal systems. All sensory information except
olfactory input must pass through the thalamus and synapse
before further processing by the cerebral cortex for conscious
interpretation of the outside world. Table 1-8 contains a
summary of thalamic nuclei. The sensory lemniscal input to the
thalamus terminates in four major nuclei. The ventral
posterolateral (VPL) nucleus receives epicritic
somatosensory input from the body via the medial lemniscus and
the fast component of pain and temperature sensation via the
direct spinothalamic tract. Nucleus VPL then projects this
information to the postcentral gyrus of the parietal lobe
of the cerebral cortex (except to the lateral portion). The
ventral posteromedial (VPM) nucleus receives epicritic
sensation, temperature sensation, and fast pain sensory
information from the head via the trigeminothalamic tracts and
taste information via the solitariothalamic projections. Nucleus
VPM projects this information to the lateral portion of the
postcentral gyrus of the parietal cortex. The lateral
geniculate body (LGB) (or lateral geniculate nucleus)
receives visual input from the ganglion cell layer of the retina
via the optic tract and conveys this information to the
primary visual cortex on the banks of the calcarine
fissure via the geniculocalcarine tract (optic
radiation). The medial geniculate body (MGB) receives
auditory input via the brachium of the inferior colliculus and
conveys this information to the transverse gyrus of Heschl of
the temporal lobe at the edge of the lateral fissure via the
auditory radiation. An additional thalamic nucleus, the
pulvinar, has part of its projection directed to a
sensory cortical structure. The pulvinar receives visual input
from the superior colliculus and projects to the visual
association cortex of the occipital lobe.
The thalamus also projects motor and autonomic information to
the cortex. The ventrolateral (VL) nucleus receives
information from the dentate nucleus of the cerebellum and from
the globus pallidus of the basal ganglia and projects fibers to
the motor cortex on the precentral gyrus of the frontal
lobe. The ventral anterior (VA) nucleus receives input
mainly from the globus pallidus and projects fibers to the
premotor cortex of the frontal lobe. The precentral gyrus
and the premotor cortex are major regions of origin of the
corticospinal and corticobulbar tracts, and cortical outflow to
brain stem UMN systems such as the red nucleus. The anterior
nuclei (ANT) receive input from the limbic system
(particularly the mammillary bodies of the hypothalamus) and
project axons carrying visceral information to the anterior
cingulate cortex.
In addition to major sensory, motor, and visceral-autonomic
projection nuclei, the thalamus also contains association
nuclei that project to association areas of the cerebral
cortex. The pulvinar projects to widespread areas of
parietal, occipital, and temporal cortex near the supramarginal
and angular gyri. The lateral dorsal (LD) nucleus
projects fibers to the posterior cingulate cortex while the
lateral posterior (LP) nucleus projects fibers to the
posterior portion of the parietal cortex. The medial dorsal
(MD) nucleus sends fibers to the prefrontal cortex
and plays an important role in maintaining the social,
intellectual, and personality related functions of prefrontal
cortex. All of the projection nuclei of the thalamus, including
the association nuclei, receive reciprocal projections from the
region of cortex to which they themselves project. Therefore,
the cerebral cortex can monitor and influence its own thalamic
input.
Finally, the thalamus contains nonspecific nuclei that
project only diffuse and sparse fibers to the cortex. They
receive input from the reticular formation of the brain stem and
from each other and are associated with maintenance of
consciousness. They are also instrumental in the conscious
interpretation of painful stimuli of deep, long-lasting nature.
The main nuclei in this category are the centromedian
nucleus, intralaminar nuclei, and reticular nucleus of
the thalamus. These nuclei can arouse the cerebral cortex
through local connections to the specific projection nuclei and
perhaps also through very sparse cortical connections. These
nuclei, along with nucleus MD, contain enkephalins and
B-endorphin and may mediate the affective or interpretative
aspects of pain.
b. Hypothalamus
The hypothalamus lies ventral to the thalamus and surrounds
the third ventricle. The nuclei of the hypothalamus fall into
two main groups: nuclei that are part of the neuroendocrine
system and nuclei that regulate autonomic and visceral
activities such as feeding, drinking, reproduction, and
thermoregulation. The neurosecretory nuclei, the supraoptic
(SON) and paraventricular (PVN) nuclei, send axons
into the posterior pituitary, where they release the hormones
vasopressin (anti-diuretic hormone, ADH) and oxytocin into the
general circulation. Additional nuclei from widespread areas of
hypothalamus (including the PVN) and other CNS regions release
hormonal-releasing factors (or hormones) and inhibiting factors
into the hypophyseal portal system at the contact zone of the
median eminence. These factors either increase or decrease
the release of anterior pituitary hormones into the blood. The
arcuate and periventricular nuclei project dopaminergic
fibers to the median eminence, where they may influence the
release of releasing factors. In addition, dopamine itself may
act as the prolactin inhibitory factor. Numerous other fiber
systems (serotonin, substance P, and other peptide systems) also
converge on the median eminence to influence the release of the
releasing factors. B-Endorphin cell bodies in a zone adjacent to
the arcuate nucleus (periarcuate region) send
opioid-containing terminals to widespread regions of the CNS,
where B-endorphin may mediate a wide range of humoral, visceral,
affective, or cognitive functions.
Visceral regulatory areas are not always organized into
discrete nuclei, and are therefore called areas, although the
designation of hypothalamic areas is an oversimplification that
has the danger of inaccurate attribution of function to areas
based on gross lesion or stimulation studies. The anterior
hypothalamic area contributes to the regulation of the
parasympathetic nervous system, while the posterior
hypothalamic area contributes to the regulation of the
sympathetic nervous system. Hunger and thirst and satiety in
eating and drinking involve activity of the dorsomedial,
ventromedial, and lateral hypothalamic nuclei or areas. The
preoptic area contributes to thermoregulation and to the
regulation of sexual function, along with the anterior
hypothalamic area. In addition, the suprachiasmatic nucleus
and the medial preoptic area regulate cyclic activity
of the hypothalamus, particularly associated with hormonal
outflow. The mammillary nuclei in the caudal hypothalamus
are major integrative centers for limbic system connections,
receiving input from the hippocampus and projecting to the
anterior thalamic nucleus. The hypothalamus also participates in
reproductive and social behavior through limbic connections with
the amygdala, the septum, limbic midbrain structures, and
regions of cortex. This places the hypothalamus in a role as the
final zone of limbic convergence.
Some hypothalamic nuclei (such as PVN, and also lateral,
dorsal, and posterior regions) send projections to the
interomediolateral cell column of the spinal cord and to the
vagal complex of the medulla (dorsal motor nucleus of X and
nucleus solitarius), thus regulating directly the outflow of
autonomic information from the brain stem and spinal cord. A
nucleus such as the PVN, thus appears to be highly complex; it
has some direct axonal projections to the posterior lobe of the
pituitary, some axonal projections to the contact zone of the
median eminence, and some descending projections to autonomic
preganglionic neurons. These three functional roles for the PVN
appear to be regulated from separate neuronal areas that
probably are interconnected. Immunocytochemical studies suggest
that at least 25 neurotransmitter-specific cell groups co-exist
in this single nucleus, PVN, often scattered and intermixed with
each other. Thus, a single nucleus may be a highly complex
region of integration for a host of neuroendocrine and visceral
functions, with many sub-components.
2. Telencephalon
The telencephalon is made up of four major systems: (1) the
olfactory system, (2) the limbic system, (3) the basal ganglia,
and (4) the neocortex.
a. The Olfactory System
The olfactory system is represented by the olfactory nerve
(called cranial nerve I, despite the fact that it is actually a
CNS tract and not a nerve), the olfactory bulb, the olfactory
tract, and an associated area of primitive cortex called the
olfactory cortex of the temporal lobe (uncus). In addition,
several limbic forebrain subcortical nuclei receive olfactory
input, such as the amygdala, septum anterior perforated
substance, and anterior olfactory nucleus. The additional
connections are numerous and complicated, and are beyond the
scope of this neuroanatomical overview. Olfaction is the only
sensory system that bypasses the thalamus to enter cerebral
cortex directly. Olfaction evolved as a system with important
direct connections to limbic forebrain structure. Olfaction
plays an important role in feeding and reproductive behavior in
many animals and has retained these connections in the course of
evolution of the human brain.
b. The Limbic System
The limbic system consists of the following groups of
structures:
1. Midbrain tegmental structures called the limbic midbrain
area.
2. The lateral hypothalamus and selected thalamic
nuclei in the diencephalon.
3. Limbic forebrain structures, including non-cortical
(amygdala, septum, nucleus basalis, and anterior perforated
substance, also called the olfactory tubercle) and
cortical (hippocampal formation, parahippocampal cortex,
periamygdaloid cortex, cingulate cortex, and prefrontal cortex)
areas.
The limbic system controls emotional responsiveness and
expression, short-term memory, and responsiveness of the
visceral and endocrine hypothalamus. The limbic system provides
an individual interpretive response to the outside world and the
inside world, releasing the animal from mandatory, built-in,
stereotyped responses to stimuli. This system works in concert
with other areas of the cerebral cortex to achieve complex
behavioral activity and responses. The nuclei and tracts of the
limbic system function as a single, holistic system. It is
difficult, if not impossible, to specify an exact function for
each component of the limbic system. The nuclei and tracts do
not function autonomously, but depend upon activity in the total
limbic circuitry for any part of the system to function
properly. However, a few limbic forebrain structures have been
implicated in playing a major role of a few specific functions.
The hippocampal formation is necessary for consolidation of
short-term memory. The amygdala can regulate emotional
responsiveness in the form of docility on one hand or rage on
the other. The periamygdaloid cortex can regulate sexual
responsiveness. The cholinergic projections of the nucleus
basalis to the cerebral cortex are thought to regulate aspects
of short-term memory and some cognitive functions, and are
thought to be deficient in the brains of some patients with
Alzheimer's disease. However, these structures still
interact with other limbic structures, and utilize
limbic-hypothalamic connections to achieve the expression of
such forms of behavior.
c. Basal Ganglia (Corpus Striatum)
The basal ganglia (nuclei) form a phylogenetically old
motor system often described as being involved in maintenance
and programming of stereotyped, repetitive, and routine motor
behavior. The basal ganglia consist of the striatum, made
up of the caudate nucleus and the putamen, and the
pallidum, consisting of the globus pallidus.
The striatum and pallidum have close, reciprocal relationships
with the substantia nigra and the subthalamus,
respectively. The subthalamus and substantia nigra often are
considered to be nuclei associated with the basal ganglia. The
basal ganglia outflow, directed from the globus pallidus,
influences motor activity through UMN systems, particularly
through projections to the ventrolateral thalamic nucleus, which
projects to cells of origin in the precentral gyrus of the
corticospinal system. The basal ganglia also work in concert
with the cerebral cortex to achieve control over voluntary motor
activities. The basal ganglia suppress unwanted movements and
enhance desired patterns of movement. The basal ganglia
therefore work closely with the neocortex, and indeed have
evolved to a highly complex and sophisticated level in the human
brain. It is probably best not to think of the basal ganglia as
an old system merely concerned with stereotyped and repetitive
movements. Rather, the highly evolved structure and function of
the basal ganglia and their role in aiding neocortical motor
activity should be kept in mind. It also is not appropriate to
think of the basal ganglia as strictly a motor system. Indeed, a
large input to the head of the caudate nucleus arises from
limbic cortex and is directed back to such structures through
connections with the globus pallidus, while the putamen received
information more from true motor regions and is interconnected
with them back through the globus pallidus. It is likely that
the basal ganglia serve an integrative function that aids the
cerebral cortex in a wide range of its activities.
d. Neocortex
The neocortex is a mantle of gray matter containing six
sheets of cells in a laminated pattern. The entire cortical
mantle consists of four major lobes: (1) frontal lobe, (2)
parietal lobe, (3) temporal lobe, and (4) occipital lobe
(see Figs. 1-29 and 1-30). An additional region of cortex, the
insula, is sometimes considered to be a fifth lobe of
cerebral cortex, but its reported visceral functions are
presently poorly understood. The neocortex is the highest center
for both voluntary motor activity and sensory integration and
interpretation. It is a center for both understanding and
initiating speech and written language. The neocortex enables
humans to anticipate the future and to remember the distant
past, including the ability to pass information from generation
to generation. In addition, the neocortex is the neurological
source of personality and is also thought to be the source of
the highest mental capabilities and intellectual achievements of
the human brain. The ability to describe perfectly the function
of neocortex would require a perfect understanding of the
complexity of human personality, human behavior and its
pathology, and interaction of humans with each other, spanning
the range of disciplines from psychology to sociology and
history. This represents perhaps the most complex and
frustrating task of neurobiology, to explain human behavior and
its peculiarities and alterations in terms of neuronal
structure, function, and chemistry.
IV. SYSTEMIC, NEUROANATOMY
As with the regional neuroanatomy section, all structures
discussed in the systemic consideration are labeled in standard
neuroanatomy atlases. In addition, many of the systems described
in this section also are summarized in schematic diagrams, the
purpose of which is to provide the reader with an overall
representation of the connections and flow of information in
that system.
A. Sensory Systems
1. Somatosensory System
Sensory information enters the nervous system when a receptor
in the periphery is stimulated sufficiently to send an
electrical impulse into the central nervous system (CNS). The
receptor is a sensory transducer that changes mechanical, heat,
or light energy into electrical energy in the form of an
electrical potential in the sensory neuron. Information passes
along the primary afferent axon toward the CNS. The cell bodies
of these primary sensory neurons are found in sensory ganglia
located outside the CNS. For spinal nerves, these ganglia are
the dorsal root ganglia, located on the dorsal root near the
spinal cord. The sensory cranial nerves have sensory ganglia
that also are peripheral, located on the cranial nerve either
close to the brain stem or at a distance, near the sensory
receptors. These ganglia will be discussed in the appropriate
sensory sections. The axons of primary somatosensory neurons
enter the spinal cord, synapse with secondary sensory neurons,
and form three types of functional secondary sensory
connections, called channels: (1) reflex channels, (2)
cerebellar channels, and (3) lemniscal channels.
a. Reflex Channels
Reflexes exist in several forms. The simplest is the
monosynaptic reflex. In this reflex, the incoming primary
sensory axon terminals, whose cell bodies are in the dorsal root
ganglia, synapse directly on a lower motor neuron (LMN) in the
anterior horn of the spinal cord. The muscle stretch reflex is
an example of a monosynaptic reflex, in which the stretch of a
tendon (quadriceps tendon in the knee jerk reflex) excites a
primary sensory group Ia axon, which synapses on a lower motor
neuron innervating the muscle whose tendon was stretched
(quadriceps), resulting in the contraction of that muscle (the
knee jerk). Other reflexes in the spinal cord are polysynaptic,
requiring the participation of interneurons. These reflexes may
function within the same segment of the spinal cord as the
sensory input or may involve many segments. For example,
withdrawal reflexes elicited by touching a hot object require
participation of many interneurons at both local and distant
spinal levels compared to the input. These reflexes can even
extend upward into the neuroaxis to influence LMNs of the motor
cranial nerve nuclei. An example of this is stepping on a tack,
resulting in the entire body withdrawing from the stimulus,
requiring the movement of skeletal muscles in the body and in
the head and neck.

b. Cerebellar Channels
Information going to the cerebellum from the somatosensory
system (Fig. 1-34) comes mainly from proprioceptive receptors in
the muscles and tendons but can arise from virtually all types
of sensory receptors. Information concerning the state of
contraction of individual muscle fibers travels mainly along Ia
afferent fibers from muscle spindles into the spinal cord, where
it synapses with cells of origin of the dorsal spinocerebellar
tract (DSCT) in Clarke's nucleus and with the cells of origin of
the cuneocerebellar tract in the lateral (accessory) cuneate
nucleus of the medulla. Information reporting the state of
contraction of whole muscles (tension on tendons) travels mainly
along Ib afferent fibers from Golgi tendon organs (GTOs) into
the spinal cord, where it synapses with the cells of origin of
the ventral spinocerebellar tract (VSCT) (border cells) and the
rostral spinocerebellar tract (RSCT) (centrobasal nucleus) in
the dorsal and intermediate spinal gray. Proprioceptive
information from the body at level T6 and below travels in the
dorsal spinocerebellar tract and the ventrospinal cerebellar
tract. Proprioceptive information from the body above level T6
travels in the cuneocerebellar tract and the rostral
spinocerebellar tract.

Cells of the dorsal spinocerebellar tract receive primary
sensory afferents mainly from muscle spindle Ia afferents from
levels T6 and below. These afferents enter the spinal cord
synapsing in Clarke's nucleus in the gray matter at the medial
base of the dorsal horn of the thoracic spinal cord. (This
nucleus is actually present from levels T1 to L2.) Cells of
Clarke's nucleus send ipsilateral projections that ascend in the
peripheral zone of the dorsal half of the lateral funiculus of
the spinal cord and enter the cerebellum through the inferior
cerebellar peduncle.
Cells of the ventral spinocerebellar tract receive primary
sensory afferents mainly from GTO Ib afferents from levels T6
and below. These afferents enter the cord and synapse with cells
in the lateral portion of the intermediate gray known as border
cells (of Cooper-Sherrington). These cells send projections
across the midline of the spinal cord in the anterior white
commissure at the level of entry of the primary sensory fibers.
The crossed secondary sensory fibers ascend in the peripheral
zone of the ventral half of the lateral funiculus of the spinal
cord and in the lateral white matter of the rhombencephalon to
the level of the rostral pons, where most of them enter the
cerebellum through the superior cerebellar peduncle. A majority
of these fibers then re-cross the midline to terminate
ipsilateral to the source of the primary sensory input
Cells of the cuneocerebellar tract receive mainly primary
sensory muscle spindle Ia afferent fibers from levels above T6.
These afferents enter the cord and ascend ipsilaterally in the
dorsal funiculus to the lateral cuneate nucleus of the medulla,
where they synapse. The cells of the lateral cuneate nucleus
project fibers ipsilaterally through the cuneocerebellar tract
into the cerebellum via the inferior cerebellar peduncle; these
cells are close enough to the ICP that their axons merge with
the ICP, and do not form a bundle that is a discrete entity that
can be described in a cross section.
Cells of the rostral spinocerebellar tract receive mainly
primary sensory GTO Ib afferents form levels above T6, which
enter the spinal cord and synapse with cells at the base of the
intermediate gray matter (centrobasal nucleus). These cells give
rise to fibers of the rostral spinocerebellar tract, which
ascends ipsilaterally and enters the cerebellum through the
inferior cerebellar peduncle.
In addition to the four direct spinocerebellar pathways,
there are two indirect spinocerebellar pathways, a
spino-olivo-cerebellar system and a spinoreticulo-cerebellar
system. In the inferior olivary system, some primary sensory Ia,
II, and Ib afferents enter the spinal cord and synapse in the
intermediate gray. Fibers from the intermediate gray cross the
midline and ascend to the inferior olivary nucleus, where they
synapse. Inferior olivary cells send olivocerebellar fibers
across the midline, where they enter the cerebellum through the
inferior peduncle. It should be kept clearly in mind that the
inferior olivary nucleus receives input from areas other than
the spinal cord, such as the red nucleus and cerebral cortex.
The inferior olivary nucleus therefore serves as a feedback
mechanism for the cerebellum integrating a wide range of sensory
and motor information from widespread areas of the CNS (see Fig.
1-34).
In the lateral reticular system, flexor reflex afferents and
a wide variety of cutaneous informations from all four
extremities enter the cord and synapse in the intermediate gray.
The intermediate gray cells then project ascending fibers to the
lateral reticular nucleus. The lateral reticular nucleus also
receives input from sources other than the spinal cord;
therefore it is also an integrating system. The large receptor
fields (from all four extremities) of these cells also emphasize
the integrative nature of this nucleus.
It should be noted that the vast majority of cerebellar input
from spinal sources is ipsilateral. Therefore, cerebellar
lesions result in symptoms on the same side as the lesion. With
truncal ataxia, the patient will fall toward the side of the
cerebellar lesion (if the lesion is only unilateral). A lesion
of one cerebellar hemisphere or one superior cerebellar peduncle
will result in an ipsilateral intention tremor, ipsilateral
dysmetria, loss of coordination, loss of rapid alternating
movements, and past-pointing (the inability to accurately reach
for, or point directly to, a target).
c. Leminiscal Channels
Conscious sensory information is processed through lemniscal
pathways from the periphery to secondary sensory nuclei and then
via lemniscal pathways to the thalamus. These thalamic nuclei
then convey this information to the cortex, either by direct
projections (from the ventral posterolateral nucleus [VPL]) or
indirectly through nonspecific nuclei of the thalamus. Both
light moving touch and pain sensations are considered lemniscal
even though some of their projections do not travel in discrete
pathways through the brain stem and do not actually reach the
thalamus directly, especially in the case of slow pain.
Epicritic: modalities from the body such as fine
discriminative touch, pressure, joint position, two-point
discrimination, and vibratory sensation travel in a true
lemniscal system called the dorsal column system (Fig. 1-35).
Primary sensory afferents come mainly from skin, hair follicles,
paccinian corpuscles, and joints. These fibers enter the spinal
cord through the dorsal roots and travel in the dorsal columns
of the dorsal funiculus, where they ascend toward their
secondary sensory nuclei in the medulla. Fibers entering the
spinal cord below T6 ascend in the fasciculus gracilis and
fibers entering at T6 and above ascend in the fasciculus
cuneatus. The primary sensory input is somatotopically arranged,
with input from the feet ascending most medially and input from
the cervical region ascending most laterally. In the medulla,
primary sensory afferents from below T6 traveling in fasciculus
gracilis synapse in nucleus gracilis, while those from T6 and
above traveling in fasciculus cuneatus synapse in nucleus
cuneatus. Additional sensory information processed through
dorsal horn interneurons is conveyed to the nuclei gracilis and
cuneatus through the dorsolateral funiculus, providing an
additional route through the spinal cord white matter for joint
position, vibratory sensation, and cutaneous sensation to reach
the dorsal column nuclei. Nuclei gracilis and cuneatus give rise
to axons that decussate in the medulla, just rostral to the
decussation of the pyramids, as the internal arcuate fibers;
these crossed fibers then ascend toward the thalamus as the
medial lemniscus, a topographically organized bundle. Medial
lemniscus fibers synapse in the ventral posterolateral (VPL)
nucleus of the thalamus. This nucleus projects to the central
and medial portions of the postcentral gyrus of the parietal
lobe. This entire lemniscal system remains somatotopically
arranged all the way from the spinal cord to the cortex. In the
cortex, information from the feet terminates most medially in
the paracentral lobule, while information from cervical
levels terminates more laterally, on the convexity of the
postcentral gyrus.

The very specific and direct lemniscal pathway of the dorsal
column system contrasts with some of the
spinothalamic-spinoreticular pathway (Fig. 1-36) carrying
protopathic information (pain, temperature, and light moving
touch). Protopathic receptors are generally free nerve endings
or small myelinated fibers. Some small myelinated fibers
(A-delta fibers) enter the spinal cord in the dorsal roots and
terminate on cells of laminae V and I. These spinal cord cells
send fibers across the midline in the anterior white commissure
that ascends in the spinothalamic tract in the ventrolateral
white matter of the spinal cord. These secondary sensory axons
ascend to the nucleus VPL of the thalamus, which in turn sends
fibers to the postcentral gyrus. This direct lemniscal portion
of the protopathic system reports temperature sensation and
so-called fast pain. Fast pain is the first sensation of injury
or pain, is accurately localized, and does not last longer than
the duration of the stimulus. The slow, excruciating pain,
outlasting the stimulus, travels by a more polysynaptic route.
It is this pain that is so dismaying and difficult to relieve in
medical practice.

Unmyelinated axons (C-fibers) of the primary sensory cells,
conveying slow pain, enter the spinal cord through the medial
portion of the dorsal root, traverse Lissauer's zone above the
dorsal horn and either enter the gray matter and synapse at the
level of entry, or ascend or descend for a segment or two before
entering the gray matter and synapsing. The primary afferents
synapse in the dorsal horn, mostly in substantia. gelatinosa
(laminae II and III). Cells of substantia gelatinosa project to
deeper layers of the dorsal horn called the nucleus proprius
(laminae IV and V). Fibers from nucleus proprius and fibers from
cells of the intermediate gray (lamina VII), to which nucleus
proprius cells project, cross the midline in the anterior white
commissure and ascend in the spinal cord in the anterolateral
funiculus as the spinothalamic-spinoreticular tracts.
The cells of origin of those systems are the targets of
considerable convergence and divergence in the spinal cord. The
true spinothalamic tract projects to the ventral posterolateral
nucleus of the thalamus, but most of the fibers in the
anterolateral funiculus system, particularly the spinoreticular
fibers, never reach the thalamus directly. Instead, they end in
the reticular formation.
After many synapses with interneurons of the spinal cord,
which tend to diffuse the stimulus, the fibers eventually enter
the spinoreticular portion of the spinothalamic-spinoreticular
system and ascend toward the reticular formation. In the
reticular formation, many collaterals are given off, further
diffusing the signals. From the reticular formation, the
information is carried to the inferior colliculus,
periaqueductal gray, other mesencephalic "pain-processing"
regions, and to nonspecific nuclei of the thalamus. The pain
information may be transmitted to the cortex directly via the
diffuse projections from the nonspecific nuclei, and also may
reach the cortex indirectly through intrathalamic connections
with direct projection nuclei of the thalamus. The cortex then
interprets activation of the reticular formation as
excruciating, persistent, sometimes poorly localized, long-term
pain. In addition to the crossed spinoreticular fibers that
synapse in the reticular formation, ipsilateral fibers also
enter the reticular formation. C-fibers enter the spinal cord
and synapse in substantia gelatinosa. Polysynaptic channels
carry the information diffusely into the ipsilateral reticular
information. Thus, the reticular formation receives diffuse
input from both ipsilateral and contralateral projections that
derive from a variety of spinal cord neuronal pools. This
account for the futility and ineffectiveness of tractotomies and
lesions induced to alleviate chronic pain in humans in all but
terminal patients. Despite severing of the anterolateral white
matter of the cord to alleviate contralateral intractable pain,
the pain usually returns in several months. Pain has perhaps the
most widespread and diffuse ascending channels to the forebrain
of any sensory modality. A system that evolved for quick,
adaptive responses to noxious stimuli has carried forward such a
strong evolutionary legacy that it often defies even the best
efforts of medical technology today.
A final comment about the spinothalamic-spinoreticular system
is warranted. Some textbooks describe a separate lateral
spinothalamic tract carrying pain, and a ventral spinothalamic
tract carrying light moving touch and temperature. This
subdivision is somewhat artificial and results from a partial
separation of both modalities and somatotopic levels. It is
therefore best to think of the protopathic channel in the
anterolateral funiculus as the combined
spinothalamic-spinoreticular system. This system conveys the
direct fast pain fibers (spinothalamic), some of the diffuse
slow pain fibers (spinoreticular), fibers conveying temperature,
and fibers conveying light moving touch. This last modality was
noted in patients with lesions of the dorsal funiculus. When
this epicritic system was destroyed, patients could still detect
touch from a light wisp of cotton moved across the body.
2. Trigeminal Sensory System
The trigeminal sensory system (Fig. 1-37) is a rostral
continuation of the somatosensory system. All trigeminal primary
sensory cell bodies, except those innervating muscle spindles,
are located in the trigeminal, or semilunar, ganglion, outside
the brain stem. Reflexes mediated through this system are both
monosynaptic and polysynaptic. The monosynaptic reflexes travel
via Ia muscle spindle afferents of cranial nerve V (for
example, for the jaw jerk reflex), and are conveyed through the
mesencephalic nucleus of V. Polysynaptic reflexes include those
mediated through other cranial nerve motor nuclei, such as the
blink reflex mediated through afferents of cranial nerve V and
through LMNs of the facial nerve (VII) nucleus. There is also a
cerebellar channel for the trigeminal system. Primary afferents
from the semilunar ganglion synapse in the main sensory nucleus
and the descending nucleus of V whose projections then enter the
cerebellum, mainly through the inferior peduncle. A few
trigeminocerebellar fibers also enter through the superior
cerebellar peduncle.

The primary sensory afferent fibers conveying epicritic
information for conscious interpretation have their cell bodies
in the semilunar ganglion just outside the mid pons. The primary
sensory axons project to a secondary sensory nucleus, the main
sensory nucleus of V. Fibers from the main sensory nucleus
ascend as the dorsal trigeminal thalamic tract (DTTT), probably
to the contralateral ventral posteromedial nucleus of the
thalamus (VPM). The fibers of nucleus VPM then project to the
most lateral aspect of the postcentral gyrus of the parietal
lobe just lateral to the region of postcentral gyrus receiving
fibers from the upper extremity through nucleus VPL of the
thalamus.
Primary sensory afferent fibers projecting protopathic
information for conscious interpretation also have their cell
bodies in the semilunar ganglion. They project mainly to the
descending nucleus of V, especially the most caudal portion of
it. This nucleus extends from the mid-pons caudally to the upper
few levels of spinal cord. Cells of this nucleus send fibers
carrying sensations of fast pain, temperature, and some
cutaneous information to nucleus VPM of the thalamus in the
crossed ventral trigeminothalamic tract (VTTT). Some additional
crossed projections from cells of the main sensory nucleus of V
convey epicritic trigeminal information to nucleus VPM via the
VTTT. Many axonal projections of neurons in the descending
nucleus of V terminate in the reticular formation and never
reach the thalamus directly, and, like the
spinothalamic-spinoreticular system, send diffuse information
into the lateral reticular formation, where it is joined by
sensory input from all other sensory systems. The somatosensory
system and the trigeminal sensory system are therefore similar
in the projection of fibers for conscious interpretation of
cutaneous sensation to the thalamus via direct lemniscal
channels and to the reticular formation via polysynaptic
connections for the processing of slow pain.
The modalities that travel in the trigeminal system arise
from receptors found in the face, the oral cavity, the anterior
two thirds of the tongue (general sensation, not taste), the
teeth, the nasal cavity, the paranasal sinuses, and part of the
meninges. General sensation from the pharynx and posterior 1/3rd
of the tongue also distributes with nerve IX to the descending
nucleus of V.
3. Visual System
The retina, in the inner posterior curve of the eye, contains
the photoreceptors, the rods and cones, that process
visual information. The cones transduce color vision and the
rods transduce black and white images. Light enters the eye by
passing through the transparent cornea, then continues
through the anterior chamber of the eye, which contains
aqueous humor, passes through the lens, where it is
further refracted and passes through the vitreous body,
which contains a gelatinous but transparent fluid. The light
passes through all the layers of the retina and strikes
the visual pigments in the photoreceptors, which are protected
by a melanin-pigmented layer to avoid dispersion and
backscatter. The cone’s cluster in the central region of the
retina, the macula (the fovea centralis in the center of the
macula, in which only cones are found), the region struck by
light from an object fixed by the eye. These cones are
responsible for color images for daylight vision (photopic
vision). The rods are particularly abundant in the
peripheral zones of the retina and are responsible for night
vision (scotopic vision). When light strikes a
photoreceptor, it alters the conformational structure of the
visual pigment in the outer segment of the photoreceptor,
resulting in a change in ionic conductance in the photoreceptor.
In the case of rods, the 11-cis retinal portion of the pigment
rhodopsin is transformed to all transretinal,
which alters the Ca++ conductance in the rod. This in
turn alters the Na+ conductance, setting up a
receptor potential. The photoreceptor actually hyperpolarizes
when light transduction occurs, resulting in a decrease in
neurotransmission compared to the constant transmitter release
apparently occurring in the dark. The pigments are located in
stacked discs in the outer segment of the photoreceptor.
In the retina, the visual message is sent through a vertical
arrangement of cells. The photoreceptors communicate with
bipolar cells, which in turn project to the ganglion cells
in the innermost layer of the retina. An additional horizontal
organization of horizontal cells and amacrine cells adds
local processing of visual information in the retina. Many of
the retinal elements communicate with graded potentials rather
than action potentials and can produce either depolarization or
hyperpolarization in the next neuron in line. Only in ganglion
cell axons, the main outflow of retina, are action potentials
consistently seen. The ganglion cells give rise to the optic
nerve, optic chiasm, and optic tract, successively (Figs.
1-38 and 1-39). Optic tract fibers project directly to the
lateral geniculate body (LGB) of the thalamus. The patterns
of crossed and uncrossed fibers depend on the area of the retina
in which the ganglion cell is located. Ganglion cells on the
temporal (outside) half of the retina project uncrossed fibers
to the ipsilateral lateral geniculate body (Fig. 1-38). Ganglion
cells on the nasal (inside) half of the retina project crossed
fibers to the contralateral lateral geniculate body. The area of
crossing fibers is a prominent landmark on the ventral surface
of the hypothalamus, called the optic chiasm. The tracts
leaving the chiasm are called the optic tracts. The optic
tract therefore contains projections carrying visual information
from the contralateral half of the visual world (visual
field) (Fig. 1-39). The LGB then projects to the primary
visual cortex (area 17) in the occipital lobe on the banks
of the calcarine fissure through the optic radiation’s
in the posterior-most portion of the posterior limb of the
internal capsule. The optic radiation’s spread out through the
parietal and temporal lobes as they pass around the lateral
walls of the occipital pole of the lateral ventricles. Fibers
carrying information from the upper retina (lower visual
fields) project through the parietal lobe to the upper
bank of the calcarine fissure, while fibers carrying
information from the lower retina (upper visual fields)
project through the temporal lobe in Myer's loop to the
lower bank of the calcarine fissure. Each of these zones
of upper or lower visual information in the cortex can be
selectively damaged, producing a contralateral visual quadrant
deficit (called quadrantanopsia).


The optic tract also projects fibers to the superior
colliculus, which is primarily responsible for visual reflex
responses by sending information to the cervical spinal cord via
the tectospinal system in the descending limb of the medial
longitudinal fasciculus. The superior colliculus also sends
tectocerebellar fibers through the superior peduncle to the
cerebellar cortex. In addition, the superior colliculus sends
fibers to the pulvinar of the thalamus, which in turn projects
to associative areas of visual cortex in the occipital lobe,
areas of 18 and 19. These projections are thought to tell
where an object is in the visual field, while the lateral
geniculate body projections are thought to tell what that
object is, and to provide for a fine-grain analysis of the
outside visual world. The optic tract also projects to the
pretectum, which conveys fibers bilaterally to the nucleus
of Edinger-Westphal, resulting in the pupillary light reflex
through the efferent III nerve projections to the ciliary
ganglion and the ciliary ganglion projections to the pupillary
constrictor muscle. Additional optic tract input synapses in the
suprachiasmatic nucleus of the hypothalamus, where
circadian light-dark rhythms may be influenced via supraspinal
projections to the sympathetic TI-T2 intermediolateral cell
column. The superior cervical ganglion in turn influences the
output of the hormone melatonin from the pineal gland,
influencing gonadal maturation.
4. Auditory System
The auditory system transduce mechanical energy of sound
waves into electrical signals, which are then analyzed by the
CNS not only for tone, loudness, and mechanical phenomena but
for content related to speech and complex interpretation of the
outside world. The peripheral apparatus for transduction of
mechanical energy (Fig. 1-40) is a system of membranes, small
bones called ossicles, fluid-filled ducts, and sensitive hair
cells. The outer ear funnels the sound waves to the tympanic
membrane, which vibrates at a specific frequency according
to the energy of the sound wave striking it. This tympanic
membrane separates the outer ear from the middle ear.

The middle ear contains a chain of three small bones, the
ossicles, which connects the tympanic membrane with the oval
window of the inner ear. The malleus is
attached to the tympanic membrane and is moved by vibration of
that membrane. The malleus in turn attaches to the incus,
which moves the stapes. The stapes inserts on the oval
window and transfers the energy conducted to it through the
other ossicles to the oval window. This ossicular chain
amplifies the original vibration of the tympanic membrane and
provides a distinct and interpretable movement of the oval
window in response to a given frequency of sound waves. Two
muscles, the tensor tympani and the stapedius,
insert on the malleus and the stapes, respectively. These
muscles, innervated by the V and VII nerves, respectively, are
controlled through auditory reflex mechanisms that contract the
muscles in response to loud noises. These muscles dampen the
movement through the ossicular chain and prevent physical damage
to the peripheral auditory apparatus.
Movement of the oval window sets up a fluid wave in the
scala vestibuli, a cavity at the base of the cochlea
filled with perilymph. The cochlea is a coiled structure
in the inner ear, supported by the bony modiolus, with
fluid-filled canals running through it; the hair cells,
the true auditory transducing cells, are located in a special
region of this cochlea called the organ of Corti. The
fluid wave through the perilymph starts at the base of
the scala vestibuli, travels to the apex (called the
helicotrema) and at this point is directly continuous with
the second perilymph-filled cavity, the scala tympani. At
the base of the cochlea, the scala tympani end at the round
window. Thus the perilymph wave moves to the helicotrema and
back to the base. Between these two perilymph-filled channels,
in cross section, runs the cochlear duct, called the
scala media. This duct is filled with endolymph, a
fluid high in potassium. The basilar membrane of the
cochlear duct separates this from the scala vestibuli; on the
basilar membrane sits the organ of Corti. Another membrane,
Reissner's membrane, separates the scala tympani from the
cochlear duct. On the basement membrane sits the organ of Corti,
which contains rows of hair cells. There is an inner row of
inner hair cells and three to five outer rows of outer hair
cells. Attached to the body part of the cochlea is an additional
membrane, the tectorial membrane, whose distal portion
moves with endolymph fluid waves. The perilymph fluid wave
results in movement of the basilar membrane and sets up a fluid
wave through the endolymph.
The basilar membrane widens toward the helicotrema. Each
specific portion of the basilar membrane, from the base to the
helicotrema, responds best, with maximal displacement, to a
specific frequency of sound. The base responds best to
high-frequency sounds, while regions toward the
helicotrema respond best to low-frequency sounds. This
specific differential sensitivity to sound of specific
frequencies reflects tonotopic organization. As a
specific region of the basilar membrane is displaced, the hair
cells of the organ of Corti move with the basilar membrane
according to mechanical forces that are different from those
acting on the tectorial membrane. The hairs of the cells extend
away from the direction of the basilar membrane into the
tectorial membrane. The tectorial membrane movement in response
to the endolymph fluid waves exerts a sheering force against the
hairs, bending them. The tectorial membrane contacts the hairs
either directly or sets up fluid movement that displaces the
hairs. The deflection of the hairs sets up a charge in
electrical conductance in the hair cell. This change in
conductance, producing a graded electrical potential, releases a
neurotransmitter from the base, which excites the primary
sensory endings (corresponding to dendrites) of the primary
sensory ganglion cells.
The ganglion cells are found in the spiral of the cochlea and
are called the spiral or auditory ganglion. These
cells are bipolar neurons, with the peripheral process
innervating the hair cells and the central process entering the
CNS through the auditory or cochlear division of the VIII
nerve. See Figure 1-41 for a schematic diagram of the
auditory system. These primary afferent fibers of the VIII nerve
project ipsilaterally to the dorsal and ventral cochlear nuclei
in the pons through the cochlear portion of the VIII cranial
nerve. The dorsal cochlear nucleus gives rise to fibers that
cross the midline in the dorsal and intermediate acoustic stria
and ascend in the lateral lemniscus. The ventral cochlear
nucleus projects fibers that cross in the ventral acoustic stria
through the trapezoid body and ascending the lateral lemniscus.
The cochlear nuclei also send uncrossed fibers, which either
synapse with the superior olivary nucleus or ascend into the
lateral lemniscus. The lateral lemniscus fibers synapse in the
inferior colliculus. The inferior colliculus projects through
the brachium of the inferior colliculus to the medial geniculate
body of the thalamus, which in turn projects to the primary
auditory cortex in the temporal lobe on the transverse gyrus of
Heschl. Other brain stem nuclei, such as the nuclei of the
lateral lemniscus and nuclei of the trapezoid body, are
interposed in the projection system of the lateral lemniscus.

One nucleus of particular importance is the superior olivary
nucleus in the pons. The medial portion of this nucleus has
"rabbit-ear cells" that receive information from both sides of
the cochlear apparatus and act to integrate the temporal
sequence of sound striking each ear at a slightly different
time. Nuclei of the lateral lemniscus and nuclei of the
trapezoid body also receive indirect auditory projections and
send fibers into both the ipsilateral and contralateral lateral
lemniscus. Therefore the auditory lemniscal channel is both
crossed and uncrossed and shows repeated re-crossing at each
level of auditory connections. This explains why a unilateral
lesion in the ascending auditory pathway does not produce
contralateral deafness but only decreased hearing in general.
However, auditory nerve damage or cochlear damage will produce
unequivocal one-sided deafness ipsilateral to the lesion.
At each step of the auditory pathway, reciprocal descending
projections are found. One particularly prominent connection
runs from the superior olivary nucleus to contact the hair cells
or primary afferent endings on the hair cells. This system, the
olivocochlear bundle, can modulate the transmission of
auditory information that enters the CNS.
5. Vestibular system
The vestibular system consists of two sets of receptors in
the inner ear that communicates information about angular
acceleration and linear acceleration into the CNS.
This information aids the brain in the interpretation of the
direction of gravitation and the direction of movements through
space. One set of receptors is found in the cristae
ampullares of the semicircular canals (or ducts), while the
other set is found in the maculae of the utricle and saccule
(Fig. 1-42). There are three semicircular canals on either side
of the body in the inner ear: a lateral canal, a
posterior canal, and an anterior canal. These canals
are all at right angles to each other, like the X, Y, and Z
planes in solid geometry. If a patient's head is tilted forward
30 degrees, the lateral canals are parallel to the ground. This
pair of lateral canals works together. The anterior canal of one
side works in conjunction with, and is parallel to, the
posterior canal of the other side. The canals are filled with
endolymph and are in continuity with the endolymph of the
cochlear duct through a thin ductus reuniens. Each canal
has an enlarged region called the ampulla. Hair cells sit
in the base of the ampulla and are collectively called the
crista. The hairs of the hair cells protrude upward into a
gelatinous wedge, called the cupula. The cupula extends
approximately one third of the way into the ampulla. As the head
moves, the endolymph drags behind as the canal moves (much like
a driver is pushed back into the car set during acceleration and
is thrown forward with braking). As the endolymph moves
differentially with regard to the canal, the cupula is bent and
the hairs are moved. This movement produces a change in hair
cell conductance, which is communicated to the primary
sensory nerve endings through use of a neurotransmitter. This
information reported by the canals is angular acceleration and
is transient. During a slow banking of a plane, a pilot has
differential endolymph movement only for approximately 20
seconds. After this period, the endolymph and canals are
rotating at the same velocity, interpreted by the CNS as a
stationary position. Therefore the canals report changes in the
position of the head and are transient sensory receptors. All
six canals must operate properly for correct interpretation of
head movements; one side balances, and works together
with, the other side. Damage to the canals or the vestibular
nerve reporting this information on one side will produce a
vestibular imbalance. The patient often will feel as if he or
his environment is moving abnormally or inappropriately, usually
in a spinning motion (called vertigo).

The second type of vestibular receptor is found in two
enlarged sac-like structure, the utricle and the saccule. These
sacs are filled with endolymph, also connected with the
endolymph in the semicircular canals. In the base of these sacs
are maculae, containing hair cells. Sitting on these
hairs are calcium carbonate structures, similar to small
pebbles, called statoliths, or otoconia. These
statoliths produce pressure on the hairs, with resultant
alterations ionic conduction in the hair cells, which in turn is
transmitted to the primary sensory nerve endings. The utricle is
oriented so that maximal stimulation occurs with upright
posture. In addition, some investigators believe that the
saccule responds to low-frequency vibrations. These stimuli
report the direction of the gravitational field (linear
acceleration) through statolith stimulation of the hair cells.
These hair cells do not adapt to statolith stimulation and are
therefore different from the transient and adaptable hair cells
in the cristae ampullares of the semicircular canals. The
utricle and saccule report linear acceleration continuously (are
non-adapting), as long as the statoliths stimulate the
hairs of the hair cells.
The primary sensory information concerning angular
acceleration from the semicircular ducts, and linear
acceleration from the utricle and saccule, travels through
cranial nerve VIII, the vestibular portion. See Figure 1-43 for
a schematic diagram of the vestibular system. The cell bodies of
these bipolar primary sensory afferents are located in
Scarpa's ganglion (vestibular ganglion). These ganglion
cells send peripheral processes to innervate the hair cells in
the cristae ampullares of the semicircular canals and the
maculae of the utricle and saccula; they also send central
axonal processes to the four vestibular nuclei and directly to
the flocculonodular lobe of the cerebellum. The vestibular
nuclei send projections to the cerebellum through the medial
portion of the inferior cerebellar peduncle, the juxtarestiform
body. These projections coordinate the position of the body in
space with the state of contraction and tension on the muscles.
Other secondary sensory vestibular projections ascend in the
medial longitudinal fasciculus to the motor nuclei of cranial
nerves III, IV, and VI, for coordination control of eye
movements during changes in head position. Distortion of one
side of the vestibular input results in an imbalance in the MLF
system, producing a rhythmic oscillatory movement in the eyes,
called nystagmus. It also is possible that conscious
sense of vestibular stimulation can be detected through
projections from the vestibular nuclei to the medial geniculate
body and subsequent MGB projections to regions of temporal
cortex. The vestibular nuclei also send fibers into the
reticular formation, where reflex responses related to nausea,
vomiting, and other characteristics of vestibular malfunction
are initiated.

Two of the vestibular nuclei also send UMN projections to the
spinal cord. The lateral vestibular nucleus conveys ipsilateral
control over extensor muscles of the body via the lateral
vestibulospinal tract. The medial vestibular nucleus conveys
control over muscles of the neck that maintain the head in space
through the medial vestibulospinal tract projections to LMNs in
the upper cervical spinal cord.
6. Visceral Sensory System
The primary sensory afferents carrying taste information
(Fig. 1-44A) from taste buds (which contain
chemoreceptors responsive to molecular stimulation) and
travel through the following cranial nerves: (1) nerve VII
through projections of the geniculate ganglion from the
anterior two thirds of the tongue, (2) nerve IX through
projections of the petrosal ganglion from the posterior
one third of the tongue, and (3) nerve X through projections of
the nodose ganglion from the epiglottis. This information
is conveyed through the solitary tract in the medulla
into the nucleus of the solitary tract, a secondary sensory
nucleus. This nucleus in turn projects crossed fibers to nucleus
VPM of the thalamus through the solitariothalamic tract. Nucleus
VPM of the thalamus projects to the lateral aspect of the
postcentral gyrus of the parietal lobe, overlapping the
trigeminal system projections through this same thalamic
nucleus. As a result, taste information from the tongue and
epiglottis overlaps the cortical zone of projections of facial
and oral cavity sensation. The nucleus solitarius also sends
projections to the parabrachial nuclei of the pons;
nuclei that are interconnected with the hypothalamus (nucleus
PVN), central amygdaloid nucleus, and other visceral processing
regions. This system of projections may permit the affective
interpretation of taste to be integrated into the hypothalamic
mechanisms that in turn regulate visceral behavior. Some reflex
visceral information (Fig. 1-44B) is also sent to the nucleus of
the solitary tract, particularly through the IX and X nerves.
For example chemoreceptive information from the carotid body
and baroreceptive information from the carotid sinus
travel via the IX nerve and the solitary tract in the medulla to
the synapse in the nucleus of the solitary tract. The nucleus of
the solitary tract in turn conveys this reflex information to
preganglionic autonomic neurons of the vagal complex for reflex
regulation of cardiovascular and respiratory responses.

Visceral pain information (Fig. 1-44C) is not
associated with the nucleus of the solitary tract. It enters the
spinal cord and is processed in the same way as other pain
sensation, through both crossed and uncrossed spinoreticular
projections. It also should be noted that general sensation of
the pharynx and posterior palate is conveyed to the descending
nucleus of V and not to the nucleus of the solitary tract.
The olfactory system is sometimes considered to be a
visceral sensory system. However, this system has intimate
association with the limbic system, is not processed through the
brain stem and thalamus, and is most appropriately discussed in
the section on the limbic system.
B. Motor Systems
1. Lower Motor Neurons
LMNs of the spinal cord send axons through the ventral roots
and peripheral nerves directly to striated muscles, where the
release of acetylcholine regulates the contraction of the
muscle. These neurons depend upon two kinds of input to maintain
their activity and subsequent muscle tone: (1) sensory input via
reflex connections; (2) UMN supraspinal regulation of tone,
posture, and voluntary movements. LMNs innervating muscles of
the body are located in the ventral horn of the spinal cord and
are subdivided into two categories. The large alpha-motor
neurons directly innervate extrafusal striated muscle fibers and
are under control of both sensory input and supraspinal systems.
The smaller gamma-motor neurons innervate intrafusal fibers of
the muscle spindles and are mainly under control of supraspinal
system. LMNs innervating skeletal muscles of the head and neck
are located in the motor cranial nerve nuclei. These nuclei are
the motor nuclei of III, IV and VI for extraocular muscles, V
for muscles of mastication, VII for muscles of facial
expression, nucleus ambiguus for palatopharyngeal and laryngeal
muscles, XI for trapezius and sternocleidomastoid muscles, and
XII for muscles of the tongue.
2. Upper Motor Neurons
UMNs communicate with LMNs either directly through
monosynaptic connections or indirectly through interneurons
located near the LMNs (Fig. 1-45). These upper motor neurons
direct and control the lower motor neurons, individually or as
groups, and achieve behavioral responses through an integrated
activity.

The cortex is the source of the two UMN systems. The first is
the corticospinal tract (Fig. 1-46). It originates in the
cerebral cortex from premotor cortex of the frontal lobe (30
percent), from the motor strip of the precentral gyrus (30
percent), and from the sensory cortex of the postcentral gyrus
of the parietal lobe (40 percent). Cells of these cortical areas
send fibers through the corona radiata, a fan-like array
of fibers, into the posterior limb of the internal
capsule in the forebrain, and through the middle three
fifths of the cerebral peduncles of the
mesencephalon. In the basis pontis, these fibers are
broken up into numerous small bundles. They recondense in the
pyramids of the medulla. At the caudal-most end of the
medulla, 80 to 90 percent of the fibers cross the midline as the
decussation of the pyramids. The crossed fibers
continue as the lateral corticospinal tract in the lateral
funiculus of the spinal cord. The uncrossed portions of the
fibers descend in the anterior corticospinal tract in the
anterior (ventral) funiculus down to all levels of the spinal
cord. A majority of these anterior corticospinal fibers then
cross through the anterior white commissure and synapse
contralateral to the cortical cells of origin. Perhaps it is the
small percentage of corticospinal tract fibers that remain
ipsilateral all the way to their terminations that therapeutic
intervention utilizes in rehabilitation of some stroke patients
and some recovery from forebrain injuries. The corticospinal
tract terminates heavily in cervical spinal cord segments (about
55 percent), corresponding to control of LMNs that innervate
hands and finger musculature. The corticospinal control heavily
influences fine flexor movements associated with skilled hand
and finger movements. The thoracic, lumbar, and sacral spinal
cord levels receive the other 45 percent of the corticospinal
connections. In the human, 90 percent of the corticospinal
fibers synapse indirectly on interneurons while the other 10
percent synapse directly on LMNs. In non-primates, the
corticospinal tract synapses entirely with interneurons. Direct
corticospinal connections with LMNs are a recent evolutionary
development seen in primates only, and appear to confer a
greater control over finger and thumb musculature. These
movements are essential for tool use and fine dexterous motor
acts.

The corticobulbar system (Fig. 1-47) arises from the
lateral regions of the same cortical areas as the corticospinal
system and travels along with the corticospinal system to the
brain stem. However, corticobulbar fibers pass through the
genu of the internal capsule rather than the posterior limb.
This tract distributes crossed fibers to the lower part of the
facial nucleus supplying muscles of the lower face, both crossed
and uncrossed fibers to nuclei of cranial nerves V and XII, both
crossed and uncrossed fibers to the upper half of the facial
nucleus supplying muscles of the upper face, and to the other
motor cranial nerve nuclei. The result is bilateral cortical
control of most of these motor nuclei. Therefore, damage to
descending corticobulbar fibers on one side of the brain (genu
of internal capsule) usually results in a palsy of only the
lower facial muscles, because the other LMNs of the cranial
nerve nuclei still can be controlled by connections from the
undamaged side. In some individuals, the V and XII nerve nuclei
also receive mainly crossed corticobulbar fibers; damage to
corticobulbar fibers on one side will result in deviation of the
tongue or the jaw, when protruded, to the side opposite the
lesion. Only bilateral corticobulbar damage will leave all of
the motor cranial nerve nuclei with loss of UMN control (called
pseudobulbar palsy).

A major flexor UMN system originates in the brain stem.
The rubrospinal tract (Fig. 1-48) arises from the red
nucleus in the ventral tegmentum of the midbrain. The
rubrospinal fibers cross the midline in the ventral tegmental
decussation, at the level of emergence from the red nucleus,
and synapse mainly indirectly through interneurons with LMNs
throughout the spinal cord. The rubrospinal tract exerts a bias
toward LMNs to flexor skeletal muscles. In this way, it
reinforces and augments the flexor bias of the corticospinal
tract, particularly in movements of the extremities. The motor
cortex also innervates the red nucleus in a topographic manner,
thus exerting control over its flexor counterpart, the
rubrospinal system. So to some extent, the rubrospinal system
and its cortical control can be thought of as an "indirect"
corticospinal tract.

The vestibulospinal system (Fig. 1-49) consists of two
tracts. The first tract is the lateral vestibulospinal tract
(Fig. 1-49A) that originates in the lateral vestibular
nucleus. It synapse’s both directly and indirectly with
ipsilateral LMNs throughout the cord and exerts a powerful
extensor bias. This tract is important in the maintenance of
antigravity tone and upright posture. The second tract is the
medial vestibulospinal tract (Fig. 1-49B). It originates in
the medial vestibular nucleus and synapses directly with
ipsilateral LMNs of the cervical region of the spinal cord,
which innervates muscles of the neck.

Two reticulospinal tracts (Fig. 1-50) originate in the
rhombencephalon. Cells of origin of the pontine
reticulospinal tract (Fig. 1-50A) reside in the reticular
formation in the caudal and rostral pontine reticular nuclei.
This tract projects to interneurons in the spinal cord mainly on
the ipsilateral side and aids the lateral vestibulospinal system
in maintaining extensor tone. The medullary reticulospinal
tract (Fig. 1-50B) originates in the reticular formation of
the medulla in nucleus reticularis gigantocellularis, synapses
with interneurons of the spinal cord mainly on the ipsilateral
side, and aids in the maintenance of flexor tone, thus
augmenting the effects of the rubrospinal and corticospinal
tracts. Both of the reticulospinal tracts are mainly
ipsilateral; they are the only UMN tracts that are not
specifically somatotopically organized.

The bulbospinal systems are important in maintaining
basic muscle tone and posture through the LMNs. In the pons, the
fibers come principally from locus coeruleus and in the medulla,
a lesser number of fibers arise from the lateral and dorsal
tegmentum. These fibers use norepinephrine as a transmitter.
Additional pontine and medullary fibers come from the raphe
nuclei (nucleus raphe magnus, obscurus, and pallidus) and use
serotonin as a transmitter. The exact role of these
noradrenergic and serotonergic fibers in maintaining the
activity of LMNs has not yet been worked out. However, they do
seem to be important for the proper functioning of the LMNs in
maintenance of tone, perhaps acting as neuromodulators,
augmenting or dampening the effects of other neurotransmitters.
All of the brain stem UMN systems receive either direct
(rubrospinal, reticulospinal) or indirect (vestibulospinal,
bulbospinal) input from the cerebral cortex, with the possible
exception of the pontine reticulospinal system. The red nucleus
may mediate influences from higher structures on the lateral
vestibular nucleus. Thus the cerebral cortex influences LMNs not
only through the corticospinal and corticobulbar tracts, but
also through corticorubrospinal, corticoreticulospinal, and
corticobulbospinal connections.
3. Cerebellum
The cerebellum functions by comparing existing motor behavior
with newly initiated behavior and smoothes and coordinates the
resulting movement through connections with the cells of origin
of the UMN systems (Fig. 1-51). The cerebellum receives its
sensory input mostly through the inferior peduncle; these enter
from the dorsal, rostral, and cuneocerebellar tracts, from the
inferior olive and the lateral reticular nuclei, and from the
vestibular and reticular nuclei. Cortical input synapses first
in the pontine nuclei, which send projections to the
contralateral cerebellar cortex through the midline cerebellar
peduncle. A few inputs from the ventral spinocerebellar tract
and from trigeminocerebellar and tectocerebellar projections
enter the cerebellum through the superior cerebellar peduncle.
The cerebellum integrates this sensory and motor input to smooth
and coordinate muscle activity through communication with upper
motor neurons.

Purkinje cells in the vermis of the cerebellum project to the
fastigial nucleus and also directly project to the lateral
vestibular nucleus at the medullopontine junction through the
juxtarestiform body to the vestibular and reticular nuclei that
send upper motor neuronal projections to the spinal cord lower
motor neurons.
Purkinje cells in the paravermis project to the globose and
emboliform nuclei, which in lower animals are merged into a
single interpositus nucleus. These nuclei send projections
through the superior peduncle principally to the red nucleus,
and also to the ventrolateral nucleus of the thalamus and
reticular nuclei of the brain stem.
Purkinje cells in the cerebellar hemisphere’s project to the
dentate nucleus, which sends its outflow through the superior
peduncle to the ventrolateral nucleus of the thalamus.
Additional dentate fibers terminate in the red nucleus. Nucleus
VL of the thalamus then directly regulates the cortical cells,
which give rise to some of the cells of origin of the
corticospinal. and corticobulbar systems, as well as the
corticorubrospinal, corticoreticulospinal, and
corticobulbospinal systems. Thus, the outflow of the entire
cerebellum is heavily directed toward the UMNs through the
outflow of the deep nuclei. The cerebellum achieves control of
movement through regulation of these brain stem and cortical
systems, which have direct control over the LMNs. The cerebellar
outflow is not directed exclusively towards motor regulation.
The fastigial nucleus exerts a prominent effect on blood
pressure, and probably acts through the reticular formation to
regulate some visceral functions. The integrated circuitry for
this regulation is not understood well.
4. Basal Ganglia
The basal ganglia are composed of the caudate nucleus, the
putamen, and the globus pallidus (the pallidum). The caudate
nucleus and putamen together make up the striatum. These nuclei
are developmentally, anatomically, and neurochemically quite
similar. The striatum (see Fig. 1-52 for a schematic diagram)
receives input from all lobes of the cerebral cortex,
from the centromedian nucleus of the thalamus, from the
pars compacta of the substantia nigra via the
nigrostriatal pathway, a dopamine pathway, and from the
raphe nuclei of the midbrain via an ascending
serotonergic pathway. The striatum has reciprocal
connections with the substantia nigra via a striatonigral
pathway that uses GABA and perhaps Substance P as its
transmitters, terminating in pars reticulata of substantia
nigra. The main output of the striatum terminates in the globus
pallidus. Some of these striatal projections use enkephalins as
their transmitters. The globus pallidus also receives input from
the subthalamus via the subthalamic fasciculus and
communicates back to the subthalamus via the
pallido-subthalamic pathway. Thus, two caudally placed
nuclei have reciprocal interactions with the basal ganglia, the
substantia nigra with the striatum and the subthalamic nucleus
with the pallidum. These connections are apparently important in
suppressing unwanted activities of the basal ganglia. When
substantia nigra is damaged in humans, Parkinson's disease
results, with muscular rigidity, a resting tremor, and
bradykinesia (a slowness of initiating voluntary movements).
When the subthalamic nucleus is damaged in humans,
hemiballismus (wild uncontrolled flailing movements of the
limbs) results.

The major output of the basal ganglia is directed through the
pallidum. The globus pallidus projects to the ventrolateral and
ventral anterior nuclei of the thalamus, as well as to the
nonspecific centromedian nucleus of the thalamus. These
pallidothalamic projections travel via the ansa lenticularis
(looping under the internal capsule) and the lenticular
fasciculus (traveling through the internal capsule), which
then join the thalamic fasciculus to terminate in the
thalamus. The globus pallidus also sends polysynaptic descending
projections into the brain stem through the pallidotegmental
tract.
The activity of the basal ganglia is integrated with the
thalamus, cerebellum, and cortex to regulate motor movements.
The thalamus, particularly the ventrolateral nucleus, receives
communication from the globus pallidus, the dentate nucleus of
the cerebellum, and the red nucleus, although probably to
separate fields of neurons in this nucleus. The thalamus then
sends information to UMNs of the cortex, which modulate the
outflow of the vital cortical motor neurons. Therefore both the
cerebellum and the basal ganglia influence motor outflow through
connections with UMNs. The basal ganglia are reported to
participate in the initiation and control of stereotyped,
repetitive movements. However, the function of the basal ganglia
is best considered as an adjunct to the cortex, through which
they can maintain a focus on desired voluntary movements and can
suppress superfluous unwanted movements. The basal ganglia are
so thoroughly integrated with other motor components of the CNS
that it is easier to explain dysfunction than function. Damage
to the cerebellum or the basal ganglia and its associated nuclei
result in involuntary motor disorders such as tremor, rigidity,
incoordination, and involuntary movements. These motor phenomena
result from altered activity in the affected structure, which in
turn alters the activity of the UMNs to which it projects, and
the subsequent LMNs under the regulation of those altered UMN
systems. Pathology of the cerebellum and basal ganglia clearly
illustrate the point that neuronal damage often can be reflected
in a patient's actions or activities only through subsequent
altered activity or dysfunction of long chains of neurons. For
example, substantia nigra damage results in motor problems of
the limbs through the dysfunction of a chain of at least six
neurons, out to the peripheral motor apparatus.
C. Visceral and Neuroendocrine Systems
1. Pituitary and Median Eminence
The pituitary gland is composed of two major lobes, the
anterior lobe (adenohypophysis) and the posterior lobe
(neurohypophysis). The posterior pituitary contains the
terminals of neurosecretory cells from the supraoptic and
paraventricular nuclei, which release vasopressin and oxytocin
directly into the blood. The anterior pituitary has few direct
neuronal connections from the hypothalamus; instead, the
median eminence of the hypothalamus acts as a zone
(hypophyseotrophic zone) in which releasing and
inhibitory factors are secreted into primary capillaries of
the hypophyseal-portal system, which transports these
factors to the anterior pituitary where they activate or inhibit
the release of hormones into the blood.
The median eminence and the releasing factor neurons are
controlled by hypothalamic inputs that influence the release of
these factors and by other brain stem and forebrain systems
whose projections influence the outflow of the releasing or
inhibitory factors. The other regulatory systems influencing the
median eminence include peptide systems, catecholamine systems,
and serotonin systems.
2. Hypothalamus
The nuclei and areas of the hypothalamus can be divided into
two functional but overlapping groups, the neuroendocrine
centers and the visceral regulatory centers. The neuroendocrine
centers include parts of the supraoptic and paraventricular
nuclei, which release vasopressin and oxytocin from terminals in
the posterior pituitary. The arcuate and periventricular nuclei,
which send dopaminergic fibers to the contact zone of the median
eminence to influence the release of releasing or inhibitory
factors, and many neurons that produce releasing or inhibitory
factors that are released from axonal projections to the contact
zone of the median eminence. Some of these releasing and
inhibitory factor neurons have their cell bodies outside the
hypothalamus.
The visceral regulatory nuclei of the hypothalamus include
the posterior hypothalamic area, the anterior hypothalamic area,
the mammillary nuclei, the dorsomedial and ventromedial nuclei,
the lateral hypothalamic area, the preoptic nuclei, and the
suprachiasmatic nucleus. The posterior hypothalamic area
regulates some sympathetic activities through the descending
projections of the medial forebrain bundle. The anterior
hypothalamic area regulates some parasympathetic activities via
projections to the midbrain through the dorsal longitudinal
fasciculus. Both of these autonomic regulatory areas of the
hypothalamus are regulated by input from the limbic forebrain.
In addition, some zones of PVN, the dorsal, lateral, and
posterior hypothalamus send direct fiber projections to the
spinal cord intermediolateral cell column, and the vagal complex
to regulate preganglionic autonomic outflow directly.
The mammillary nuclei of the hypothalamus form a major
connection in the limbic system. They receive input from the
hippocampus via the fornix. These nuclei also receive input from
the mesencephalic tegmentum through the mammillary peduncle.
The mammillary nuclei send projections to the anterior nucleus
of the thalamus via the mammillthalamic tract, forming
part of Papez's circuit of limbic activity. The
mammillary nuclei also send outflow to the mesencephalic
tegmentum through the mammilotegmental tract, which it is
integrated with other descending hypothalamic influences that
terminate in the mesencephalic tegmentum and exert control over
the autonomic nervous system and motor nuclei.
The dorsomedial and ventromedial nuclei have been implicated
in feeding behavior. The input to this area comes from the
limbic forebrain. Output goes through both the medial forebrain
bundle and the dorsal longitudinal fasciculus to autonomic and
motor nuclei in the brain stem. There are also numerous
intrahypothalamic projections interconnecting the dorsomedial
and ventromedial nuclei with areas such as the lateral
hypothalamic area.
The lateral hypothalamic area is associated with feeding and
drinking behavior. It is also the main interconnecting zone
between the limbic forebrain and the limbic midbrain areas.
Major input from the mesencephalic tegmentum and from brain stem
monoamine nuclei arrives via the medial forebrain bundle. The
lateral hypothalamic area also receives input from olfactory
structures, orbitofrontal cortex, and septal nuclei via
descending projections of the medial forebrain bundle.
The preoptic area receives input from the amygdala via the
stria terminalis, from the orbitofrontal cortex via the
medial forebrain bundle, and from other hypothalamic nuclei.
The preoptic: output projects mainly to other hypothalamic
nuclei, where it is thought to regulate circadian and cyclic
rhythms, particularly in association with sex hormones. Both the
suprachiasmatic: and the preoptic: nuclei have been implicated
in control of circadian rhythms, the former nucleus via direct
retino-hypothalamic input carrying light-dark information. The
preoptic area also contains many thermo-sensitive neurons.
Some areas of the hypothalamus respond to interleukin-1 and
other cytokines, and respond to immunization with altered
neuronal electrical activity and monoamine metabolism,
particularly of norepinephrine. These areas may be receiving
"molecular sensory" information from the immune system, and may
be interposed in typical hypothalamic circuitry influencing the
periphery, with the novel target of mobile cells of the immune
system. Areas that participate in this neural-immune
communication include the preoptic area, dorsomedial nucleus,
and paraventricular nucleus.
It also is clear that the hypothalamus, as both a
neuroendocrine and visceral regulatory system, is an important
region of influence from the limbic: system and its connections.
This relationship is further discussed below.
3. Limbic System
The limbic: system controls emotional responsiveness and
affective behavior through the utilization of the visceral and
neuroendocrine systems of the hypothalamus. The limbic: system
consists of a midbrain portion situated in the midbrain
tegmentum. The limbic midbrain (also some areas of pons)
includes the dorsal and ventral tegmental nuclei, the
interpeduncular nucleus, and the noradrenergic: locus coeruleus,
the serotonergic central superior and dorsal raphe nuclei, the
ventrolateral periaqueductal gray, and the dopaminergic ventral
tegmental area. These areas receive integrated sensory and
visceral information from the reticular formation. The limbic
midbrain conveys the actual state of the body, both internally
and externally, to the hypothalamus and to the limbic forebrain.
The limbic forebrain projects back to the limbic midbrain,
placing the hypothalamus in a strategic position for integrating
information going in both directions. The lateral hypothalamus
subserves this major integrative position within the
hypothalamus. In addition, the limbic midbrain structures
project to many limbic forebrain areas, including the septum,
amygdala, olfactory tubercle, nucleus accumbens, cingulate and
frontal cortex, and hippocampus.
The limbic forebrain consists of both cortical and
subcortical structures. The subcortical structures include the
septum, amygdala, and basal olfactory nuclei such as the
olfactory tubercle (anterior perforated substance), nucleus
accumbens, nucleus basalis of Meynert (cholinergic) and
anterior olfactory nucleus. The cortical structures include the
hippocampus, the cingulate cortex, entorhinal cortex (including
parahippocampal and periamygdaloid cortex), and prefrontal
cortex. Most of the limbic forebrain connections channel into
the hypothalamus, where they influence both visceral
hypothalamic and neuroendocrine outflow. The individual
structures making up the limbic forebrain are difficult to
describe functionally because they act as an integrated whole.
The entire limbic forebrain must act together to achieve the
regulation of affective behavior that is normally seen. However,
a few pathways are of particular importance. The hippocampus
sends information to the mammillary bodies, the septum, and the
preoptic hypothalamus via the fornix. The nucleus basalis
sends cholinergic axonal projections to wide ranges of
cerebral cortex. The amygdala interconnects with many visceral
and neuroendocrine centers of the hypothalamus via the stria
terminalis and the direct amygdalofugal pathway
(diagonal band of Broca). The septum has a major output to the
hippocampus through the fornix and also interconnects with the
hypothalamus. The cingulate cortex also has a major influence
over the hippocampus through polysynaptic connections.
Prefrontal cortex sends projections to the anterior and preoptic
hypothalamus via the descending portion of the medial forebrain
bundle. The anterior thalamic nuclei receive input from the
mammillary nuclei (mammillthalamic tract), a major
receiving zone of the fornix. Both cerebral neocortex and the
olfactory system play a major controlling role over limbic
forebrain structures.
D. Thalamus and Neocortex
The thalamus is the major relay center to the cortex for all
sensory systems except the olfactory system for motor systems,
particularly the cerebellum and basal ganglia, and for
autonomic-visceral system through the anterior nuclei. A
discussion of the thalamic nuclei and the portions of cortex to
which they project were presented in the section on regional
neuroanatomy. Since the thalamus and cortex have reciprocal
connections and act in concert to maintain the overall activity
of the cerebral cortex, only a few functional aspects of the
cortex will be further discussed in this section.
The cerebral cortex receives information from specific
projection nuclei of the thalamus, from a few fibers of
nonspecific thalamic nuclei, from the olfactory system, from
brain stem noradrenergic, dopaminergic, and serotonergic nuclei,
and from the cholinergic nucleus basalis. The output of the
cortex includes projection fibers. The projection fibers have
been partially discussed with motor systems. The major
projection fibers of the cerebral cortex include the following
systems:
1. Corticospinal tract
2. Corticobulbar tract
3. Corticorubrospinal system
4. Corticoreticulospinal system
5. Corticobulbospinal system (polysynaptic)
6. Corticotectal fibers regulating visual reflex responses
7. Corticopontine fibers
8. Corticostriate fibers
9. Corticonuclear fibers to secondary nuclei for regulation
of sensory input
10. Corticothalamic connections with all projection nuclei
and with nonspecific thalamic nuclei
11. Cortical connections to other brain stem nuclei such as
the inferior olivary nucleus
12. Cortical connections to autonomic preganglionic neurons
in the spinal cord and brain stem, and associated control nuclei
(nucleus solitarius)
From the list above, it is clear that the neocortex. has a
connection with virtually all major subdivisions of the CNS. In
addition to projection fibers, the cortex has much
cortical intercommunication. These connections are of two types:
commissural bundles that cross the midline, and
association or arcuate fibers that interconnect cortical
areas of a single hemisphere. The commissural bundles (see Fig.
1-30) are the corpus callosum and the anterior
commissure. The corpus callosum interconnects the frontal
lobes (through the rostrum and genu), the parietal
lobes (through the body) and the temporal and occipital
lobes (through the body and splenium). The anterior
commissure mainly interconnects limbic forebrain structures of
the temporal lobes. Arcuate fibers are either short arcuate
fibers, interconnecting adjacent gyri, or long arcuate
fibers, interconnecting more distant areas of cortex.
One particularly interesting feature of the cortex is
lateralization of function. The two hemispheres are not
identical. One of the hemispheres, the dominant hemisphere,
controls both the understanding and the interpretation of
language and the motor initiation of speech. In 98 percent of
humans, the dominant hemisphere is the left hemisphere.
Broca's area in the frontal lobe is the area of motor
control, or expressive control of speech. Also, on the
parietotemporal border of the dominant hemisphere is
Wernicke's area, the receptive area for speech. Loss of
these areas renders a person unable to initiate speech or to
understand speech, respectively (called expressive and
receptive aphasia, respectively). Although Broca's area and
Wernicke's area are described as separate regions, they really
represent a continuum of cortex involved in language function.
Control of writing and reading of language is also under
principal control of the dominant hemisphere, in more posterior
areas of parietotemporal cortex. Damage here may result in
dyslexia or dysgraphia. The non-dominant hemisphere
processes geometric and spatial relationships. Recent data also
suggest that the dominant auditory cortex play a major role in
musical interpretation and appreciation. Thus, both the dominant
and non-dominant (or the conversant and non-conversant)
hemispheres must work together to achieve a final interpretation
of the outside world and to achieve a full complement of human
skills and behavior.
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MEDICAL NEUROBIOLOGY
INDIANA UNIVERSITY SCHOOL OF MEDICINE
TERRE HAUTE CENTER FOR MEDICAL EDUCATION
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