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:

1. Fine, discriminative touch, vibration, two-point discrimination, stereognosis (the ability to determine the size, shape, and texture of an object by tough alone)
2. 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)

1. Pain (both fast, localized pain and slow, excruciating, poorly localized pain)
2. Temperature
3. Light moving touch

c. Special Senses

1. Vision
2. Olfaction
3. Audition
4. Vestibular proprioception, the position of the head in space (linear and angular acceleration)
5. Taste

1. Painful sensation from the viscera
2. 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.

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.

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.

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.

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.

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.

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

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.

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.

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.

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.

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.

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.

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.

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.

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).

1. 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.
2. Upper Motor Neurons. The cell bodies are located in the brain stem; the axons descend to the LMNs and associated interneurons, which they control.
3. 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.

1. 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).
2. 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.
3. 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.

1. 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.
2. 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