Responding Organ or Tissue	Effect of Sympathetic Nervous System*	Effect of Parasympathetic Nervous System†
Heart	↑ Rate and strength of heartbeat (β-receptors)	↓ Rate and strength of heartbeat
Smooth muscle of blood vessels
• Skin blood vessels	Constriction (α-receptors)	No effect
• Skeletal muscle blood vessels	Dilation (β-receptors)	No effect
• Coronary blood vessels	Dilation (β-receptors), constriction (α-receptors)	Dilation
• Abdominal blood vessels	Constriction (α-receptors)	No effect
• Blood vessels of external genitals	Ejaculation (contraction of smooth muscle in male ducts [e.g., epididymis, ductus deferens])	Dilation of blood vessels causing erection in male
Smooth muscle of hollow organs and sphincters
• Bronchi	Dilation (β-receptors)	Constriction
• Digestive tract, except sphincters	↓ Peristalsis (β-receptors)	↑ Peristalsis
• Sphincters of digestive tract	Contraction (α-receptors)	Relaxation
• Urinary bladder	Relaxation (β-receptors)	Contraction
• Urinary sphincters	Contraction (α-receptors)	Relaxation
Eye
• Iris	Contraction of radial muscle, dilation of pupil	Contraction of circular muscle, constriction of pupil
• Cilia	Relaxation, accommodation for far vision	Contraction, accommodation for near vision
Hairs (pilomotor muscles)	Contraction producing goose pimples or piloerection (α-receptors)	No effect
Glands
• Sweat	↑ Sweat (neurotransmitter, acetylcholine)	No effect
• Digestive (e.g., salivary, gastric)	↓ Secretion of saliva; not known for others	↑ Secretion of saliva and gastric HCl acid
• Pancreas, including islets	↓ Secretion	↑ Secretion of pancreatic juice and insulin
Liver	↑ Glycogenolysis (β-receptors), increase in blood glucose level	No effect
Adrenal medulla‡	↑ Epinephrine secretion	No effect

^*Neurotransmitter is norepinephrine unless otherwise stated.

^†Neurotransmitter is acetylcholine unless otherwise stated.

^‡Sympathetic preganglionic axons terminate in contact with secreting cells of the adrenal medulla. Thus the adrenal medulla functions as a “giant sympathetic postganglionic neuron.”

Modified from Thibodeau GA, Patton KT: Anatomy and physiology, ed 6, St Louis, 2006, Mosby.

A typical neuron consists of a cell body, multiple dendrites, and an axon (Fig. 56-1). The cell body containing the nucleus and cytoplasm is the metabolic center of the neuron. Dendrites are short processes extending from the cell body that receive impulses from the axons of other neurons and conduct impulses toward the cell body. The axon projects varying distances from the cell body, ranging from several micrometers to more than a meter. The axon carries nerve impulses to other neurons or to end organs. The end organs are smooth and striated muscles and glands.

FIG. 56-1 Structural features of neurons: dendrites, cell body, and axons.

Many axons in the CNS and PNS are covered by a myelin sheath, a white, lipid substance that acts as an insulator for the conduction of impulses. Axons may be myelinated or unmyelinated. Generally, the smaller fibers are unmyelinated.

Neurons have long been thought to be nonmitotic. That is, after being damaged neurons could not be replaced. The discovery of neuronal stem cells now demonstrates that neurogenesis occurs in adult brains after cerebral injury.¹

Glial Cells.

Glial cells (glia or neuroglia) provide support, nourishment, and protection to neurons. Glial cells constitute almost half of the brain and spinal cord mass and are 5 to 10 times more numerous than neurons.

Glial cells are divided into microglia and macroglia. Microglia, specialized macrophages capable of phagocytosis, protect the neurons. These cells are mobile within the brain and multiply when the brain is damaged.

Different types of macroglial cells include the astrocytes (most abundant), oligodendrocytes, and ependymal cells.² Astrocytes are found primarily in gray matter and provide structural support to neurons. Their delicate processes form the blood-brain barrier with the endothelium of the blood vessels. They also play a role in synaptic transmission (conduction of impulses between neurons). When the brain is injured, astrocytes act as phagocytes for neuronal debris. They help restore the neurochemical milieu and provide support for repair. Proliferation of astrocytes contributes to the formation of scar tissue (gliosis) in the CNS.

Oligodendrocytes are specialized cells that produce the myelin sheath of nerve fibers in the CNS and are primarily found in the white matter of the CNS. (Schwann cells myelinate the nerve fibers in the periphery.) Ependymal cells line the brain ventricles and aid in the secretion of cerebrospinal fluid (CSF).

Neuroglia are mitotic and can replicate. In general, when neurons are destroyed, the tissue is replaced by the proliferation of neuroglial cells. Most primary CNS tumors involve glial cells. Primary malignancies involving neurons are rare.

Nerve Regeneration

If the axon of the nerve cell is damaged, the cell attempts to repair itself. Damaged nerve cells attempt to grow back to their original destinations by sprouting many branches from the damaged ends of their axons. Axons in the CNS are generally less successful than peripheral axons in regeneration.³

Injured nerve fibers in the PNS can regenerate by growing within the protective myelin sheath of the supporting Schwann cells if the cell body is intact. The final result of nerve regeneration depends on the number of axon sprouts that join with the appropriate Schwann cell columns and reinnervate appropriate end organs.

Nerve Impulse

The purpose of a neuron is to initiate, receive, and process messages about events both within and outside the body. The initiation of a neuronal message (nerve impulse) involves the generation of an action potential. Once an action potential is initiated, a series of action potentials travels along the axon. When the impulse reaches the end of the nerve fiber, it is transmitted across the junction between nerve cells (synapse) by a chemical interaction involving neurotransmitters. This chemical interaction generates another set of action potentials in the next neuron. These events are repeated until the nerve impulse reaches its destination.

Because of its insulating capacity, myelination of nerve axons facilitates the conduction of an action potential. Many peripheral nerve axons have nodes of Ranvier (gaps in the myelin sheath) that allow an action potential to travel much faster by jumping from node to node without traversing the insulated membrane segment. This is called saltatory (hopping) conduction. In an unmyelinated fiber, the wave of depolarization travels the entire length of the axon, with each portion of the membrane becoming depolarized in turn.

Synapse.

A synapse is the structural and functional junction between two neurons. It is the point at which the nerve impulse is transmitted from one neuron to another. The nerve impulse can also be transmitted from neurons to glands or muscles. The essential structures of synaptic transmission are a presynaptic terminal, a synaptic cleft, and a receptor site on the postsynaptic cell.

Neurotransmitters.

Neurotransmitters are chemicals that affect the transmission of impulses across the synaptic cleft. (Examples of neurotransmitters are presented in Table 56-1.) Excitatory neurotransmitters activate postsynaptic receptors that increase the likelihood that an action potential will be generated. Inhibitory neurotransmitters activate postsynaptic receptors that inhibit the likelihood that an action potential will be generated.

TABLE 56-1

NEUROTRANSMITTERS *

Neurotransmitter	Clinical Relevance
Acetylcholine	A decrease in acetylcholine-secreting neurons is seen in Alzheimer’s disease. Myasthenia gravis results from a reduction in acetylcholine receptors.
Amines
Epinephrine (adrenalin)	Is both a hormone and neurotransmitter. Produced in neurons of CNS and neurosecretory cells of adrenal medulla. Critical component of the fight-or-flight response of SNS.
Norepinephrine	Is both a hormone and neurotransmitter. Has important role as neurotransmitter released from SNS affecting the heart. Along with epinephrine, has important role in fight-or-flight response, increasing heart rate, triggering the release of glucose from energy stores, and increasing blood flow to skeletal muscle.
Serotonin	Primarily found in GI tract, platelets, and CNS. Involved in moods, emotions, and sleep.
Dopamine	Produced in several areas of brain. Involved in emotions and moods and regulating motor control. Parkinson’s disease results from destruction of dopamine-secreting neurons.
Amino Acids
γ-Aminobutyric acid (GABA)	Chief inhibitory neurotransmitter in CNS. Has a role in regulating neuronal excitability throughout the nervous system. Drugs that increase GABA function have been used to treat seizure disorders.
Glutamate and aspartate	Plays key role in learning and memory. Sustained release of glutamate and prolonged excitation is toxic to nerve cells. Glutamate is a destructive factor in amyotrophic lateral sclerosis.
Neuropeptides
Endorphins and enkephalins	Endogenous opioids that function as neurotransmitters. Produced in pituitary gland and hypothalamus. Produce analgesia and a feeling of well-being. The opioids morphine and heroin bind to endorphin and enkephalin receptors and produce the same effect as the endogenous opioids.
Substance P	Neurotransmitter in pain transmission pathways. Morphine blocks its release.

CNS, Central nervous system; SNS, sympathetic nervous system.

^*These are examples only. Most of the neurotransmitters are also found in other locations and may have additional functions.

Each of the hundreds to thousands of synaptic connections of a single neuron has an influence on that neuron. In general, the net effect (excitatory or inhibitory) depends on the number of presynaptic neurons that are releasing neurotransmitters on the postsynaptic cell. A presynaptic cell that releases an excitatory neurotransmitter does not always cause the postsynaptic cell to depolarize enough to generate an action potential.

Neurotransmitters can be affected by drugs and toxins, which can modify their function or block their attachment to receptor sites on the postsynaptic membrane. When many presynaptic cells release excitatory neurotransmitters on a single neuron, the sum of their input is enough to generate an action potential. Neurotransmitters continue to combine with the receptor sites at the postsynaptic membrane until they are inactivated by enzymes, are taken up by the presynaptic endings, or diffuse away from the synaptic region. With the use of cerebral microdialysis (minimally invasive sampling technique), neurotransmitter levels can now be measured in the cerebral cortex.⁴

Central Nervous System

The components of the CNS include the cerebrum (cerebral hemispheres), brainstem, cerebellum, and spinal cord.

Spinal Cord.

The spinal cord is continuous with the brainstem and exits from the cranial cavity through the foramen magnum. A cross section of the spinal cord reveals gray matter that is centrally located in an H shape and is surrounded by white matter. The gray matter contains the cell bodies of voluntary motor neurons, preganglionic autonomic motor neurons, and association neurons (interneurons). The white matter contains the axons of the ascending sensory and the descending (suprasegmental) motor fibers. The myelin surrounding these fibers gives them their white appearance. The spinal pathways or tracts are named for the point of origin and the point of destination (e.g., spinocerebellar tract [ascending], corticospinal tract [descending]).

Ascending Tracts.

In general, the ascending tracts carry specific sensory information to higher levels of the CNS. This information comes from special sensory receptors in the skin, muscles and joints, viscera, and blood vessels and enters the spinal cord by way of the dorsal roots of the spinal nerves. The fasciculus gracilis and the fasciculus cuneatus (commonly called the dorsal or posterior columns) carry information and transmit impulses concerned with touch, deep pressure, vibration, position sense, and kinesthesia (appreciation of movement, weight, and body parts). The spinocerebellar tracts carry information about muscle tension and body position to the cerebellum for coordination of movement. The spinothalamic tracts carry pain and temperature sensations. Therefore the ascending tracts are organized by sensory modality, as well as by anatomy.

Although the functions of these pathways are generally accepted, other ascending tracts may also carry sensory modalities. The symptoms of various neurologic diseases suggest that additional pathways for touch, position sense, and vibration exist.

Descending Tracts.

Descending tracts carry impulses that are responsible for muscle movement. Among the most important descending tracts are the corticobulbar and corticospinal tracts, collectively termed the pyramidal tract. These tracts carry volitional (voluntary) impulses from the cerebral cortex to the cranial and peripheral nerves. Another group of descending motor tracts carries impulses from the extrapyramidal system (all motor systems except the pyramidal) concerned with voluntary movement. It includes pathways originating in the brainstem, basal ganglia, and cerebellum. The motor output exits the spinal cord by way of the ventral roots of the spinal nerves.

Lower and Upper Motor Neurons.

Lower motor neurons (LMNs) are the final common pathway through which descending motor tracts influence skeletal muscle. The cell bodies of LMNs, which send axons to innervate the skeletal muscles of the arms, trunk, and legs, are located in the anterior horn of the corresponding segments of the spinal cord (e.g., cervical segments contain LMNs for the arms). LMNs for skeletal muscles of the eyes, face, mouth, and throat are located in the corresponding segments of the brainstem. These cell bodies and their axons make up the somatic motor components of the cranial nerves. LMN lesions generally cause weakness or paralysis, denervation atrophy, hyporeflexia or areflexia, and decreased muscle tone (flaccidity).

Upper motor neurons (UMNs) originate in the cerebral cortex and project downward. The corticobulbar tract ends in the brainstem, and the corticospinal tract descends into the spinal cord. These neurons influence skeletal muscle movement. UMN lesions generally cause weakness or paralysis, disuse atrophy, hyperreflexia, and increased muscle tone (spasticity).

Reflex Arc.

A reflex is an involuntary response to stimuli. In the spinal cord, reflex arcs play an important role in maintaining muscle tone, which is essential for body posture. The components of a monosynaptic reflex arc (Fig. 56-2) are a receptor organ, an afferent neuron, an effector neuron, and an effector organ (e.g., skeletal muscle). The afferent neuron synapses with the efferent neuron in the gray matter of the spinal cord. More complex reflex arcs have other neurons (interneurons) in addition to the afferent neuron influencing the effector neuron.

Brain.

The term brain usually refers to the three major intracranial components: cerebrum, brainstem, and cerebellum.

Cerebrum.

The cerebrum is composed of the right and left cerebral hemispheres and divided into four lobes: frontal, temporal, parietal, and occipital (Fig. 56-3). The functions of the cerebrum are multiple and complex (Table 56-2). The frontal lobe controls higher cognitive function, memory retention, voluntary eye movements, voluntary motor movement, and speech in Broca’s area. The temporal lobe integrates somatic, visual, and auditory data and contains Wernicke’s speech area. The parietal lobe interprets spatial information and contains the sensory cortex. Processing of sight takes place in the occipital lobe.

TABLE 56-2

FUNCTION OF CEREBRUM

Part	Location	Function
Cortical Areas
*Motor*
Primary	Precentral gyrus	Motor control and movement on opposite side of body
Supplemental	Anterior to precentral gyrus	Facilitates proximal muscle activity, including activity for stance and gait, and spontaneous movement and coordination
*Sensory*
Somatic	Postcentral gyrus	Sensory response from opposite side of body
Visual	Occipital lobe	Registers visual images
Auditory	Superior temporal gyrus	Registers auditory input
Association areas	Parietal lobe	Integrates somatic and sensory input
	Posterior temporal lobe	Integrates visual and auditory input for language comprehension
	Anterior temporal lobe	Integrates past experiences
	Anterior frontal lobe	Controls higher-order processes (e.g., judgment, reasoning)
*Language*
Comprehension	Wernicke’s area	Integrates auditory language (understanding of spoken words)
Expression	Broca’s area	Regulates verbal expression
Basal Ganglia	Near lateral ventricles of both cerebral hemispheres	Control and facilitate learned and automatic movements
Thalamus	Below basal ganglia	Relays sensory and motor input to and from the cerebrum
Hypothalamus	Below thalamus	Regulates endocrine and autonomic functions
Limbic System	Lateral to hypothalamus	Influences emotional behavior and basic drives such as feeding and sexual behavior

The division of the cerebrum into lobes is useful to delineate portions of the neocortex (gray matter), which makes up the outer layer of the cerebral hemispheres. Neurons in specific parts of the neocortex are essential for various highly complex and sophisticated aspects of mental function, such as language, memory, and appreciation of visual-spatial relationships.

The basal ganglia, thalamus, hypothalamus, and limbic system are also located in the cerebrum. The basal ganglia are a group of structures located centrally in the cerebrum and midbrain. Most of them are on both sides of the thalamus. The function of the basal ganglia includes the initiation, execution, and completion of voluntary movements, learning, emotional response, and automatic movements associated with skeletal muscle activity (e.g., swinging the arms while walking, swallowing saliva, and blinking).

The thalamus (part of the diencephalon) lies directly above the brainstem (Fig. 56-4) and is the major relay center for afferent inputs to the cerebral cortex. The hypothalamus is located just inferior to the thalamus and slightly in front of the midbrain. It regulates the ANS and the endocrine system. The limbic system is located near the inner surfaces of the cerebral hemispheres and is concerned with emotion, aggression, feeding behavior, and sexual response.

FIG. 56-4 Major divisions of the central nervous system (CNS).

Brainstem.

The brainstem includes the midbrain, pons, and medulla (see Fig. 56-4). Ascending and descending fibers to and from the cerebrum and cerebellum pass through the brainstem. The nuclei of cranial nerves III through XII are in the brainstem. The vital centers concerned with respiratory, vasomotor, and cardiac function are located in the medulla.

Also located in the brainstem is the reticular formation, a diffusely arranged group of neurons and their axons that extends from the medulla to the thalamus and hypothalamus. The functions of the reticular formation include relaying sensory information, influencing excitatory and inhibitory control of spinal motor neurons, and controlling vasomotor and respiratory activity. The reticular activating system (RAS) is a complex system that requires communication among the brainstem, reticular formation, and cerebral cortex. The RAS is responsible for regulating arousal and sleep-wake transitions. The brainstem also contains the centers for sneezing, coughing, hiccupping, vomiting, sucking, and swallowing.

Cerebellum.

The cerebellum is located in the posterior part of the cranial fossa inferior to the occipital lobe. The cerebellum coordinates voluntary movement and maintains trunk stability and equilibrium. The cerebellum receives information from the cerebral cortex, muscles, joints, and inner ear. It influences motor activity through axonal connections to the motor cortex, the brainstem nuclei, and their descending pathways.

Ventricles and Cerebrospinal Fluid.

The ventricles are four interconnected fluid-filled cavities. The lower portion of the fourth ventricle becomes the central canal in the lower part of the brainstem. The spinal canal extends centrally through the full length of the spinal cord.

Cerebrospinal fluid (CSF) circulates within the subarachnoid space that surrounds the brain, brainstem, and spinal cord. This fluid provides cushioning for the brain and the spinal cord, allows fluid shifts from the cranial cavity to the spinal cavity, and carries nutrients. The formation of CSF in the choroid plexus in the ventricles involves both passive diffusion and active transport of substances. CSF resembles an ultrafiltrate of blood. Although CSF is produced at an average rate of about 500 mL/day, many factors influence CSF production and absorption. The ventricles and central canal are normally filled with an average of 135 mL of CSF. Changes in the rate of production or absorption will result in a change in the volume of CSF that remains in the ventricles and central canal. Excessive buildup of CSF results in a condition known as hydrocephalus.

The CSF circulates throughout the ventricles and seeps into the subarachnoid space surrounding the brain and spinal cord. It is absorbed primarily through the arachnoid villi (tiny projections into the subarachnoid space), into the intradural venous sinuses, and eventually into the venous system.

The analysis of CSF composition provides useful diagnostic information related to certain nervous system diseases. CSF pressure is often measured in patients with actual or suspected intracranial injury. Increased intracranial pressure, indicated by increased CSF pressure, can force downward (central) herniation of the brain and brainstem. The signs marking this event are part of the herniation syndrome (see Chapter 57).

Peripheral Nervous System

The PNS includes all the neuronal structures that lie outside the CNS. It consists of the spinal and cranial nerves, their associated ganglia (groupings of cell bodies), and portions of the ANS.

Spinal Nerves.

The spinal cord can be seen as a series of spinal segments, one on top of another. In addition to the cell bodies, each segment contains a pair of dorsal (afferent) sensory nerve fibers or roots and ventral (efferent) motor fibers or roots, which innervate a specific region of the body. This combined motor-sensory nerve is called a spinal nerve (Fig. 56-5). The cell bodies of the voluntary motor system are located in the anterior horn of the spinal cord gray matter. The cell bodies of the autonomic (involuntary) motor system are located in the anterolateral portion of the spinal cord gray matter. The cell bodies of sensory fibers are located in the dorsal root ganglia just outside the spinal cord. On exiting the spinal column, each spinal nerve divides into ventral and dorsal rami, a collection of motor and sensory fibers that eventually goes to peripheral structures (e.g., skin, muscles, viscera).

A dermatome is the area of skin innervated by the sensory fibers of a single dorsal root of a spinal nerve (Fig. 56-6). The dermatomes give a general picture of somatic sensory innervation by spinal segments. A myotome is a muscle group innervated by the primary motor neurons of a single ventral root. The dermatomes and myotomes of a given spinal segment overlap with those of adjacent segments because of the development of ascending and descending collateral branches of nerve fibers.

Cranial Nerves.

The cranial nerves (CNs) are the 12 paired nerves composed of cell bodies with fibers that exit from the cranial cavity. Unlike the spinal nerves, which always have both afferent sensory and efferent motor fibers, some CNs are only sensory, some only motor, and some both.

Table 56-3 summarizes the motor and sensory components of the CNs. Fig. 56-7 shows the position of the CNs in relation to the brain and spinal cord. Just as the cell bodies of the spinal nerves are located in specific segments of the spinal cord, so are the cell bodies (nuclei) of the CNs located in specific segments of the brain. Exceptions are the nuclei of the olfactory and optic nerves. The primary cell bodies of the olfactory nerve are located in the nasal epithelium, and those of the optic nerve are in the retina.

TABLE 56-3

CRANIAL NERVES

Nerve	Connection With Brain	Function
I Olfactory	Anterior ventral cerebrum	Sensory: from olfactory (smell)
II Optic	Lateral geniculate body of the thalamus	Sensory: from retina of eyes (vision)
III Oculomotor	Midbrain	Motor: to four eye movement muscles and levator palpebrae muscle Parasympathetic: smooth muscle in eyeball
IV Trochlear	Midbrain	Motor: to one eye movement muscle, the superior oblique muscle
V Trigeminal
• Ophthalmic branch	Pons	Sensory: from forehead, eye, superior nasal cavity
• Maxillary branch	Pons	Sensory: from inferior nasal cavity, face, upper teeth, mucosa of superior mouth
• Mandibular branch	Pons	Sensory: from surfaces of jaw, lower teeth, mucosa of lower mouth, and anterior tongue Motor: to muscles of mastication
VI Abducens	Pons	Motor: to the lateral rectus of the eye
VII Facial	Junction of pons and medulla	Motor: to facial muscles of expression and cheek muscle Sensory: taste from anterior two thirds of tongue
VIII Vestibulocochlear
• Vestibular branch	Junction of pons and medulla	Sensory: from equilibrium sensory organ, the vestibular apparatus
• Cochlear branch	Junction of pons and medulla	Sensory: from auditory sensory organ, the cochlea
IX Glossopharyngeal	Medulla	Sensory: from pharynx and posterior tongue, including taste Motor: to superior pharyngeal muscles
X Vagus	Medulla	Sensory: from much of viscera of thorax and abdomen Motor: to larynx and middle and inferior pharyngeal muscles Parasympathetic: heart, lungs, most of digestive system
XI Accessory	Medulla and superior spinal segments	Motor: to sternocleidomastoid and trapezius muscles
XII Hypoglossal	Medulla	Motor: to muscles of tongue