organization and control of the nervous systemfac.ksu.edu.sa › sites › default › files ›...

UNITTenAlterations in theNervous System

CHAPTER

36 Organization and Control of the Nervous System

Nervous Tissue CellsNeuronsSupporting Cells

Supporting Cells of the Peripheral Nervous SystemSupporting Cells of the Central Nervous System

Metabolic Requirements of Nervous TissueNerve Cell Communication

Action PotentialsSynaptic TransmissionMessenger Molecules

Development and Organization of the Nervous System

Embryonic DevelopmentSegmental Organization

Cell ColumnsLongitudinal Tracts

The Spinal Cord and BrainThe Spinal CordSpinal NervesThe Brain

HindbrainMidbrainForebrain

637

MeningesVentricular System and Cerebrospinal FluidBlood-Brain and Cerebrospinal Fluid–Brain Barriers

The Autonomic Nervous SystemAutonomic Efferent Pathways

Sympathetic Nervous SystemParasympathetic Nervous System

Central Integrative PathwaysAutonomic Neurotransmission

Acetylcholine and Cholinergic ReceptorsCatecholamines and Adrenergic Receptors

T he nervous system, in coordination with the endocrinesystem, provides the means by which cell and tissue func-tions are integrated into a solitary, surviving organism. It

controls skeletal muscle movement and helps to regulate car-diac and visceral smooth muscle activity. The nervous systemenables the reception, integration, and perception of sensoryinformation; it provides the substratum necessary for intelli-gence, anticipation, and judgment; and it facilitates adjustmentto an ever-changing external environment.

NERVOUS TISSUE CELLS

The nervous system can be divided into two parts: the centralnervous system (CNS) and the peripheral nervous system(PNS). The CNS consists of the brain and spinal cord, which is

protected by the skull and vertebral column. The PNS is foundoutside these structures. Inherent in the basic design of the ner-vous system is the provision for the concentration of compu-tational and control functions in the CNS. In this design, thePNS functions as an input-output system for relaying input to the CNS and for transmitting output messages that controleffector organs, such as muscles and glands.

Nervous tissue contains two types of cells: neurons andsupporting cells. The neurons are the functional cells of the nervous system. They exhibit membrane excitability and con-ductivity and secrete neurotransmitters and hormones, such asepinephrine and antidiuretic hormone. The supporting cells,such as Schwann cells in the PNS and the glial cells in the CNS,protect the nervous system and provide metabolic support forthe neurons.

NeuronsThe functioning cells of the nervous system are called neurons.Neurons have three distinct parts: the soma or cell body and itscytoplasm-filled processes, the dendrites and axons (Fig. 36-1).These processes form the functional connections, or synapses,with other nerve cells, with receptor cells, or with effector cells.Axonal processes are particularly designed for rapid communi-cation with other neurons and the many body structures in-nervated by the nervous system. Afferent, or sensory, neuronstransmit information from the PNS to the CNS. Efferent neu-rons, or motoneurons, carry information away from the CNS(Fig. 36-1). Interspersed between the afferent and efferent neu-rons is a network of interconnecting neurons (interneurons orinternuncial neurons) that modulate and control the body’s re-sponse to changes in the internal and external environments.

The cell body of a neuron contains a large, vesicular nucleuswith one or more distinct nucleoli and a well-developed roughendoplasmic reticulum. A neuron’s nucleus has the same DNA

and genetic code content that is present in other cells of thebody, and its nucleolus, which is composed of portions of sev-eral chromosomes, produces RNA associated with protein syn-thesis. The cytoplasm contains large masses of ribosomes thatare prominent in most neurons. These acidic RNA masses,which are involved in protein synthesis, stain as dark Nissl bod-ies with basic histologic stains (see Fig. 36-1).

The dendrites (i.e., “treelike”) are multiple, branched exten-sions of the nerve cell body; they conduct information towardthe cell body and are the main source of information for theneuron. The dendrites and cell body are studded with synapticterminals that communicate with axons and dendrites of otherneurons.

Axons are long efferent processes that project from the cellbody and carry impulses away from the cell. Most neuronshave only one axon; however, axons may exhibit multiplebranching that results in many axonal terminals. The cyto-plasm of the cell body extends to fill the dendrites and theaxon. The proteins and other materials used by the axon aresynthesized in the cell body and then flow down the axonthrough its cytoplasm.

The cell body of the neuron is equipped for a high level ofmetabolic activity. This is necessary because the cell body mustsynthesize the cytoplasmic and membrane constituents re-quired to maintain the function of the axon and its terminals.Some of these axons extend for a distance of 1 to 1.5 m andhave a volume that is 200 to 500 times greater than the cellbody itself. Two axonal transport systems, one slow and onerapid, move molecules from the cell body through the cyto-plasm of the axon to its terminals. Replacement proteins andnutrients slowly diffuse from the cell body, where they aresynthesized, down the axon, moving at the rate of approxi-mately 1 mm/day. Other molecules, such as some neurosecre-tory granules (e.g., neurotransmitters, neuromodulators, andneurohormones) or their precursors, are conveyed by a rapid,energy-dependent active transport system, moving at the rateof approximately 400 mm/day. For example, antidiuretic hor-mone and oxytocin, which is synthesized by neurons in thehypothalamus, is carried by rapid axonal transport to the pos-terior pituitary, where the hormones are released into the blood.A reverse rapid (i.e., retrograde) axonal transport system movesmaterials, including target cell messenger molecules, from axo-nal terminals back to the cell body.

Supporting CellsSupporting cells of the nervous system, the Schwann and satel-lite cells of the PNS and the several types of glial cells of theCNS, give the neurons protection and metabolic support. Thesupporting cells segregate the neurons into isolated metaboliccompartments, which are required for normal neural function.Astrocytes, together with the tightly joined endothelial cells of the capillaries in the CNS, contribute to what is called theblood-brain barrier. This term is used to emphasize the imper-meability of the nervous system to large or potentially harm-ful molecules.

The many-layered myelin wrappings of Schwann cells of thePNS and the oligodendroglia of the CNS produce the myelinsheaths that serve to increase the velocity of nerve impulse con-duction in axons. Myelin has a high lipid content, which gives

638 Unit Ten: Alterations in the Nervous System

KEY CONCEPTS

THE STRUCTURAL ORGANIZATION OF THE NERVOUS SYSTEM

■ The nervous system is divided into two parts: theCNS, which consists of the brain and spinal cord,and the PNS, which contains the input and outputneurons that lie outside the CNS.

■ The neurons, which are functioning cells of the ner-vous system, consist of a cell body with cytoplasm-filled processes, the dendrites, and the axons, whichform the functional connections with other nerve or effector cells.

■ There are two types of neurons: afferent neurons orsensory neurons, which carry information to theCNS, and efferent neurons or motoneurons, whichcarry information from the CNS to the effectororgans.

it a whitish color, and the name white matter is given to the masses of myelinated fibers of the spinal cord and brain.Besides its role in increasing conduction velocity, the myelinsheath is essential for the survival of larger neuronal processes,perhaps by the secretion of neurotrophic compounds. In somepathologic conditions, such as multiple sclerosis in the CNSand Guillain-Barré syndrome in the PNS, the myelin may de-generate or be destroyed, leaving a section of the axonal processwithout myelin while leaving the nearby Schwann or oligo-dendroglial cells intact. Unless remyelination takes place, theaxon eventually dies.

Supporting Cells of the Peripheral Nervous SystemSchwann cells and satellite cells are the two types of support-ing cells in the PNS. Normally, the nerve cell bodies in thePNS are collected into ganglia, such as the dorsal root andautonomic ganglia. The cell bodies and processes of the pe-ripheral nerves are separated from the connective tissueframework of the ganglion by a single layer of flattened cap-sular cells called satellite cells. Satellite cells secrete a basementmembrane that protects the cell body from the diffusion oflarge molecules.

The processes of larger afferent and efferent neurons aresurrounded by the cell membrane and cytoplasm of Schwanncells, which are close relatives of the satellite cells. Duringmyelination, the Schwann cell wraps around the nerve pro-cess many times in a “jelly roll” fashion (Fig. 36-2). Schwanncells line up along the neuronal process, and each of these cellsforms its own discrete myelin segment. The end of each myelinsegment attaches to the cell membrane of the axon by means

639Chapter 36: Organization and Control of the Nervous System

Dendrite

Axonhillock

Initial segment

CNSPNS

AxonMyleinsheath

Nucleus ofSchwann

cell

Schwann cell myelin

NeuromuscularjunctionMuscle fiber

Nucleus

Nucleolus

Nisslbodies PNS

CNS

Synapticterminals

Afferent cell bodyin dorsal root ganglion

Free nerveendings in skin

Node of Ranvier

Oligodendroglialcell myelin

Oligodendroglialcell myelinSchwann cell

myelin

Nucleus

Nucleolus

Nissl bodies

■ FIGURE 36-1 ■ (A) Afferentand (B) efferent neurons, show-ing the soma or cell body, den-drites, and axon. Arrows indicatethe direction for conduction ofaction potential.

Axon

Layers of myelin

Schwanncellnucleus

Node ofRanvier

Axon

Layers of myelin

Schwanncellnucleus

■ FIGURE 36-2 ■ The Schwann cell forms a myelin sheath aroundthe larger nerve fibers in the peripheral nervous system. Duringmyelination, the Schwann cell wraps around the nerve processmany times in a “jelly roll” fashion. The end of each myelin seg-ment attaches to the cell membrane of the axon by means of in-tercellular junctions. Successive Schwann cells are separated byshort extracellular fluid gaps called the nodes of Ranvier, where themyelin is missing and the voltage-gated sodium channels areconcentrated.

of intercellular junctions. Successive Schwann cells are sepa-rated by short extracellular fluid gaps called the nodes of Ran-vier, where the myelin is missing and voltage-gated sodiumchannels are concentrated. The nodes of Ranvier increase nerveconduction by allowing the impulse to jump from node tonode through the extracellular fluid in a process called salta-tory conduction (from the Latin saltare, “to jump”). In this way,the impulse can travel more rapidly than it could if it were re-quired to move systematically along the entire nerve process.This increased conduction velocity greatly reduces reactiontime, or time between the application of a stimulus and thesubsequent motor response. The short reaction time is of par-ticular importance in peripheral nerves with long distances(sometimes 1 to 1.5 m) for conduction between the CNS anddistal effector organs.

Each of the Schwann cells along a peripheral nerve is en-cased in a continuous tube of basement membrane, which inturn is surrounded by a multilayered sheath of loose connec-tive tissue known as the endoneurium (Fig. 36-3). The endo-neurial sheath, which is essential to the regeneration of injuredperipheral nerves, provides a collagenous tube through whicha regenerating axon can again reach its former target. The endo-neurial sheath does not penetrate the CNS. The absence of theendoneurial sheath is thought to be a major factor in the lim-ited axonal regeneration of CNS nerves compared with thoseof the PNS.

The endoneurial sheaths are bundled with blood vessels intosmall bundles or clusters of nerves called fascicles. In the nerve,the fascicles consisting of bundles of nerve fibers are sur-rounded by another protective covering called the perineurium.Usually, several fascicles are further surrounded by the heavy,protective epineurial sheath of the peripheral nerve. The protec-tive layers that surround the peripheral nerve processes are con-tinuous with the connective tissue capsule of the sensory nerveendings and the connective tissue that surrounds the effector

structures, such as the skeletal muscle cell. Centrally, the con-nective tissue layers continue along the dorsal and ventral rootsof the nerve and fuse with the meninges that surround thespinal cord and brain.

Supporting Cells of the Central Nervous SystemSupporting cells of the CNS consist of the oligodendroglia, as-troglia, microglia, and ependymal cells (Fig. 36-4). The oligo-dendroglial cells form the myelin in the CNS. Instead of form-ing a myelin covering for a single axon, these cells reach outwith several processes, each wrapping around and forming amultilayered myelin segment around several different axons.The coverings of axons in the CNS function in increasing thevelocity of nerve conduction, similar to the peripheral myeli-nated fibers.

A second type of glial cell, the astroglia, is particularly promi-nent in the gray matter of the CNS. These large cells have manyprocesses, some reaching to the surface of the capillaries, othersreaching to the surface of the nerve cells, and still others fillingmost of the intercellular space of the CNS. The astrocytic link-age between the blood vessels and the neurons may provide atransport mechanism for the exchange of oxygen, carbon diox-ide, and metabolites. The astrocytes also have an importantrole in sequestering cations such as calcium and potassiumfrom the intercellular fluid. Astrocytes can fill their cytoplasmwith microfibrils (i.e., fibrous astrocytes), and masses of thesecells form the special type of scar tissue called gliosis that devel-ops in the CNS when tissue is destroyed.

A third type of glial cell, the microglia, is a small phagocyticcell that is available for cleaning up debris after cellular dam-age, infection, or cell death. The fourth type of cell, the epen-dymal cell, forms the lining of the neural tube cavity, the ven-tricular system. In some areas, these cells combine with a richvascular network to form the choroid plexus, where productionof the cerebrospinal fluid (CSF) takes place.


Sensory neuron

EpineuriumEndoneurium

Perineurium

Schwann cell

Myelin

Skin

Motor neuron

Striated muscle

■ FIGURE 36-3 ■ Section of a peripheralnerve containing axons of both afferent(sensory) and efferent (motor) neurons.(Modified from Cormack D.H. [1987].Ham’s histology [9th ed., p. 374]. Philadel-phia: J.B. Lippincott)

Metabolic Requirements of Nervous TissueNervous tissue has a high rate of metabolism. Although thebrain comprises only 2% of the body’s weight, it receives ap-proximately 15% of the resting cardiac output and consumes20% of its oxygen. Despite its substantial energy requirements,the brain can neither store oxygen nor engage in anaerobic me-tabolism. An interruption in the blood or oxygen supply to thebrain rapidly leads to clinically observable signs and symp-toms. Without oxygen, brain cells continue to function for ap-proximately 10 seconds. Unconsciousness occurs almost si-multaneously with cardiac arrest, and the death of brain cellsbegins within 4 to 6 minutes. Interruption of blood flow alsoleads to the accumulation of metabolic by-products that aretoxic to neural tissue.

Glucose is the major fuel source for the nervous system, butneurons have no provision for storing glucose. Ketones canprovide for limited temporary energy requirements; however,these sources are rapidly depleted. Unlike muscle cells, neu-rons have no glycogen stores and must rely on glucose fromthe blood or the glycogen stores of supporting glial cells. Per-sons receiving insulin for diabetes may experience signs ofneural dysfunction and unconsciousness (i.e., insulin reactionor shock) when blood glucose drops because of insulin excess(see Chapter 32).

NERVE CELL COMMUNICATION

Neurons are characterized by the ability to communicate withother neurons and body cells through pulsed electrical signalscalled impulses. An impulse, or action potential (discussed inChapter 1), represents the movement of electrical charge alongthe axon membrane. This phenomenon, sometimes called con-ductance, is based on the rapid flow of charged ions through theplasma membrane. In excitable tissue, ions such as sodium,potassium, and calcium move through the membrane chan-nels and carry the electrical charges involved in the initiationand transmission of such impulses.

Action Potentials Nerve signals are transmitted by action potentials, which areabrupt, pulsatile changes in the membrane potential that last afew ten thousandths to a few thousandths of a second. Actionpotentials can be divided into three phases: the resting or po-larized state, depolarization, and repolarization (Fig. 36-5).


Capillary

Astrocyte

Ependymalcells

Cerebrospinalfluid

Oligodendrocyte

Neuron

Microglial cell

■ FIGURE 36-4 ■ The cells of thecentral nervous system (CNS). Dia-grammatic view of relationships be-tween the glial elements (astrocyte,oligodendrocyte, microglial cell, andthe ependymal cells), the capillaries,the cerebral spinal fluid, and the cellbodies of CNS neurons.

In summary, nervous tissue is composed of two types ofcells: neurons and supporting cells. Neurons are composed ofthree parts: a cell body, which controls cell activity; the den-drites, which conduct information toward the cell body; andthe axon, which carries impulses from the cell body. The sup-porting cells consist of Schwann and satellite cells of the PNSand the glial cells of the CNS. Supporting cells protect and

provide metabolic support for the neurons and aid in segre-gating them into isolated compartments, which is necessaryfor normal neuronal function. The Schwann cells of the PNSand the oligodendroglial cells of the CNS form the myelinsheath that allows for rapid conduction of impulses. The ner-vous system has a high level of metabolic activity, requiring acontinuous supply of oxygen and glucose. Although the braincomprises only 2% of the body’s weight, it receives approxi-mately 15% of the resting cardiac output and consumes 20%of its oxygen.

The resting membrane potential represents the undisturbedperiod of the action potential during which the nerve is nottransmitting impulses. During this time the inside of the mem-brane is negatively charged with respect to the outside, and themembrane is said to be polarized. The resting phase of the mem-brane potential continues until some event causes the mem-brane to increase its permeability to sodium. The thresholdpotential represents the membrane potential at which neuronsor other excitable tissues are stimulated to fire. When thethreshold potential is reached, the gatelike structures in theion channels open. The gates are either fully open or fullyclosed (all-or-none). Under ordinary circumstances, the thresh-old stimulus is sufficient to open large numbers of ion chan-nels, triggering massive depolarization of the membrane (theaction potential).

Depolarization is characterized by the flow of electricallycharged ions and the reversal of the membrane potential.During the depolarization phase, the membrane suddenly be-comes permeable to sodium ions. The rapid inflow of sodiumions produces local currents that travel through the adjacentcell membrane, causing the sodium channels in this part of themembrane to open. Thus, the impulse moves longitudinallyalong the nerve, moving from one part of the axon to another.Repolarization is the phase during which the polarity of theresting membrane potential is re-established. This is accom-plished with closure of the sodium channels and opening ofthe potassium channels. The outflow of positively charged po-tassium ions across the cell membrane returns the membranepotential to negativity. The sodium-potassium pump graduallyre-establishes the resting ionic concentrations on each side ofthe membrane.

The excitability of neurons can be affected by conditionsthat alter the resting membrane potential, moving it eithercloser to or further from the threshold potential. Hypopolariza-tion increases the excitability of the postsynaptic neuron bybringing the membrane potential closer to the threshold po-tential so that a smaller subsequent stimulus is needed to causethe neuron to fire. Hyperpolarization brings the membranepotential further from threshold and has the opposite effect. It

has an inhibitory effect and decreases the likelihood that an ac-tion potential will be generated.

Synaptic TransmissionNeurons communicate with each other through structuresknown as synapses. Two types of synapses are found in the ner-vous system: electrical and chemical. Electrical synapses permitthe passage of current-carrying ions through small openingscalled gap junctions that penetrate the cell junction of adjoiningcells and allow current to travel in either direction. The gapjunctions allow an action potential to pass directly and quicklyfrom one neuron to another. They may link neurons havingclose functional relationships into circuits.

The most common type of synapse is the chemical synapse.Chemical synapses involve special presynaptic and postsynapticmembrane structures, separated by a synaptic cleft (Fig. 36-6).The presynaptic terminal secretes one and often several chem-ical transmitter molecules (i.e., neurotransmitters or neuro-modulators) into the synaptic cleft. The neurotransmitters dif-fuse into the synaptic cleft and unite with receptors on thepostsynaptic membrane. In contrast to an electrical synapse, achemical synapse serves as a rectifier, permitting only one-waycommunication. One-way conduction is a particularly impor-tant characteristic of chemical synapses. Chemical synapses aredivided into two types: excitatory and inhibitory. In excitatorysynapses, binding of the neurotransmitter to the receptor pro-duces depolarization of the postsynaptic membrane. Bindingof the neurotransmitter to the receptor in an inhibitory synapsereduces the postsynaptic neuron’s ability to generate an actionpotential. Most inhibitory neurotransmitters induce hyper-polarization of the postsynaptic membrane by making themembrane more permeable to potassium or chloride, or both(see Chapter 6).

Chemical synapses are the slowest component in progres-sive communication through a sequence of neurons, such as in


+20

0

20

40

60

80

Time(msec)

Resting potential

Threshold potential

Overshoot

Repolarization

Depolarization

Mem

bran

e po

tent

ial (

mv)

■ FIGURE 36-5 ■ Time course of the action potential recorded atone point of an axon with one electrode inside and one on the out-side of the plasma membrane.

Presynaptic neuronprocess

Mitochondrion

Synapticcleft

Excitatory transmitter vesicles

Transmittermolecules

Postsynapticneuron Postsynaptic

receptor

■ FIGURE 36-6 ■ A chemical synapse showing the synaptic vesi-cles in the presynaptic neuron, release of the transmitter, andbinding of the transmitter to the receptors on the membrane sur-face of the postsynaptic neuron.

a spinal reflex. In contrast to the conduction of electrical actionpotentials, each successive event at the chemical synapse—transmitter secretion, diffusion across the synaptic cleft, inter-action with postsynaptic receptors, and generation of a sub-sequent action potential in the postsynaptic neuron—consumestime. On average, conduction across a chemical synapse requiresapproximately 0.3 milliseconds.

A neuron’s cell body and dendrites are covered by thousandsof synapses, any or many of which can be active at any moment.Because of the interaction of this rich synaptic input, each neu-ron resembles a little integrator, in which circuits of many neu-rons interact with one another. It is the complexity of these in-teractions and the subtle integrations involved in producingbehavorial responses that gives the system its intelligence.

Messenger MoleculesNeurotransmitters are the chemical messenger molecules of thenervous system. The messenger molecules of the nervous sys-tem include the neurotransmitters, neurohumoral mediatorssuch as epinephrine, neuromodulators, and neurotrophic ornerve growth factors.

Neurotransmitters are small molecules that incorporate apositively charged nitrogen atom; they include several aminoacids, peptides, and monoamines. Amino acids are the build-ing blocks of proteins and are present in body fluids. Peptidesare low–molecular-weight molecules that are made up of twoor more amino acids. They include substance P and the endor-phins and enkephalins, which are involved in pain sensationand perception (see Chapter 39). A monoamine is an aminemolecule containing one amino group (NH2). Serotonin, dopa-mine, norepinephrine, and epinephrine are monoamines syn-thesized from amino acids. Fortunately, the blood-brain barrierprotects the nervous system from circulating amino acids andother molecules with potential neurotransmitter activity.

The process of neurotransmission involves the synthesis,storage, and release of a neurotransmitter; the reaction of theneurotransmitter with a receptor; and termination of the re-ceptor action (Fig. 36-7). Neurotransmitters are synthesized inthe cytoplasm of the axon terminal. The synthesis of transmit-ters may require one or more enzyme-catalyzed steps (e.g., onefor acetylcholine and three for norepinephrine). Neurons arelimited as to the type of transmitter they can synthesize by theirenzyme systems. After synthesis, the neurotransmitter mole-cules are stored in the axon terminal in tiny, membrane-boundsacs called synaptic vesicles. There may be thousands of vesiclesin a single terminal, each containing 10,000 to 100,000 trans-mitter molecules. The vesicle protects the neurotransmittersfrom enzyme destruction in the nerve terminal. The arrival ofan impulse at a nerve terminal causes the vesicles to move tothe cell membrane and release their transmitter moleculesinto the synaptic space.

Neurotransmitters exert their actions through specific pro-teins, called receptors, embedded in the postsynaptic membrane.These receptors are tailored precisely to match the size andshape of the transmitter. In each case, the interaction between atransmitter and receptor results in a specific physiologic re-sponse. The action of a transmitter is determined by the type ofreceptor (excitatory or inhibitory) to which it binds. For exam-ple, acetylcholine is excitatory when it is released at a myoneuraljunction, and it is inhibitory when it is released at the sinoatrialnode in the heart. Receptors are named according to the type of

neurotransmitter with which they interact. For example, a cho-linergic receptor is a receptor that binds acetylcholine.

Rapid removal of a transmitter, once it has exerted its effectson the postsynaptic membrane, is necessary to maintain precisecontrol of neural transmission. A released transmitter can un-dergo one of three fates: it can be broken down into inactive sub-stances by enzymes; it can be taken back up into the pre-synaptic neuron in a process called reuptake; or it can diffuseaway into the intercellular fluid until its concentration is toolow to influence postsynaptic excitability. For example, acetyl-choline is rapidly broken down by acetylcholinesterase intoacetic acid and choline, with the choline being taken back intothe presynaptic neuron for reuse in acetylcholine synthesis. Thecatecholamines are largely taken back into the neuron in an un-changed form for reuse. Catecholamines also can be degradedby enzymes in the synaptic space or in the nerve terminals.

Neurohumoral mediators reach their target cells through thebloodstream and produce an even slower action than do theneuromodulators. Both the nervous system and the endocrinesystem use chemical molecules as messengers. As more infor-mation is obtained about the chemical messengers of these sys-tems, the distinction between them becomes less evident. Manyneurons, such as those in the adrenal medulla, secrete transmit-ters into the bloodstream, and it has been found that other neu-rons possess receptor sites for hormones. Many hormones haveturned out to be neurotransmitters. Vasopressin (also knownas antidiuretic hormone), a peptide hormone released from theposterior pituitary gland, acts as a hormone in the kidney andas a neurotransmitter for nerve cells in the hypothalamus. Morethan a dozen of these cell-to-cell and blood-borne messengerscan relay signals in the nervous system or the endocrine system.

Other classes of messenger molecules, known as neuro-modulators, also may be released from axon terminals. Neuro-modulator molecules react with presynaptic or postsynaptic


Postsynapticneuron

Enzyme

Presynapticreceptor

Postsynapticreceptor

Reuptake

Presynapticneuron

Metabolite

12

3b3a

3c

4

T

■ FIGURE 36-7 ■ Schematic illustration of (1) neurotransmitter (T)release; (2) binding of transmitter to postsynaptic receptor; termi-nation of transmitter action by (3a) reuptake of transmitter into thepresynaptic terminal, (3b) enzymatic degradation, or (3c) diffusionaway from the synapse; and (4) binding of transmitter to pre-synaptic receptors for feedback regulation of transmitter release.

receptors to alter the release of or response to neurotransmitters.Neuromodulators may act on postsynaptic receptors to produceslower and longer-lasting changes in membrane excitability.This alters the action of the faster-acting neurotransmitter mol-ecules by enhancing or decreasing their effectiveness. By com-bining with autoreceptors on its own presynaptic membrane,a transmitter can act as a neuromodulator to augment or in-hibit further nerve activity. In some nerves, such as the periphe-ral sympathetic nerves, a messenger molecule can have bothtransmitter and modulator functions. For example, norepineph-rine can activate an α1-adrenergic postsynaptic receptor toproduce vasoconstriction or stimulate an α2-adrenergic pre-synaptic receptor to inhibit further norepinephrine release.

Neurotrophic or nerve growth factors are required to maintainthe long-term survival of the postsynaptic cell and are secretedby axon terminals independent of action potentials. Examplesinclude neuron-to-neuron trophic factors in the sequentialsynapses of CNS sensory neurons. Trophic factors from targetcells that enter the axon and are necessary for the long-term sur-vival of presynaptic neurons also have been demonstrated.Target cell-to-neuron trophic factors probably have great sig-nificance in establishing specific neural connections duringnormal embryonic development.

DEVELOPMENT AND ORGANIZATIONOF THE NERVOUS SYSTEM

The development of the nervous system can be traced far backinto evolutionary history. During its development, newer func-tional features and greater complexity resulted from the modi-fication and enlargement of more primitive structures. Survivalof the species depended on the rapid reaction to environmen-tal danger, to potential food sources, or to a sexual partner.

The front, or rostral, end of the CNS became specialized forsensing the external environment and controlling reactions toit. In time, the ancient organization, which is largely retainedin the spinal cord segments, was expanded in the forward seg-ments of the nervous system. Of these, the most forward seg-ments have undergone the most radical modification and havedeveloped into the forebrain: the diencephalon and the cere-bral hemispheres. The dominance of the front end of the CNSis reflected in a hierarchy of control levels: brain stem overspinal cord, and forebrain over brain stem. Throughout evolu-tion, newer functions were added to the surface of functionallymore ancient systems. As newer functions became concen-trated at the rostral end of the nervous system, they also be-came more vulnerable to injury.

Embryonic DevelopmentThe nervous system appears very early in embryonic develop-ment (week 3). This early development is essential because itinfluences the development and organization of many otherbody systems, including the axial skeleton, skeletal muscles,and sensory organs such as the eyes and ears. During later fetallife and thereafter, the nervous system provides communica-tion, signal processing, integrative, and memory functions. Theearly induction and later lifelong communication functions ofthe nervous system are at the center of the integrity, survival,and individuality of each person.

All body tissues and organs have developed from the threeembryonic layers (i.e., endoderm, ectoderm, and mesoderm)that were present during the third week of embryonic life (Fig. 36-8). The body is organized into the soma and viscera.


In summary, neurons are characterized by the ability tocommunicate with other neurons and body cells throughpulsed electrical signals called action potentials. The cell mem-branes of neurons contain ion channels that are responsiblefor generating action potentials. Action potentials are dividedinto three parts: (1) the resting membrane potential, duringwhich the membrane is polarized but no electrical activity occurs; the (2) depolarization phase, during which sodiumchannels open, allowing rapid inflow of the sodium ions thatgenerate the electrical impulse; and (3) the repolarizationphase, during which the membrane is permeable to thepotassium ion, allowing for the efflux of potassium ions and return to the resting membrane potential.

Synapses are structures that permit communication be-tween neurons. Two types of synapses have been identified:electrical and chemical. Electrical synapses consist of gapjunctions between adjacent cells that allow action potentialsto move rapidly from one cell to another. Chemical synapsesinvolve special presynaptic and postsynaptic structures, sepa-rated by a synaptic cleft. They rely on chemical messengers,released from the presynaptic neuron, that cross the synapticcleft and then interact with receptors on the postsynapticneuron.

Neurotransmitters are chemical messengers that controlneural function; they selectively cause excitation or inhibitionof action potentials. Three major types of neurotransmittersare known: amino acids such as glutamic acid and GABA,peptides such as the endorphins and enkephalins, and mono-amines such as epinephrine and norepinephrine. Neuro-transmitters interact with cell membrane receptors to produceeither excitatory or inhibitory actions. Neuromodulators arechemical messengers that react with membrane receptors toproduce slower and longer-acting changes in membrane per-meability. Neurotrophic or growth factors, also released frompresynaptic terminals, are required to maintain the long-termsurvival of postsynaptic neurons.

KEY CONCEPTS

HIERARCHY OF NERVOUS SYSTEM CONTROL

■ No part of the nervous system functions indepen-dently of other parts.

■ Progressively greater complexity in the responsesand greater precision in their control occur at eachhigher level of the nervous system.

■ The more rostral, recently developed parts of theneural tube gain dominance or control over lowerlevels.

■ As newer functions became concentrated at the ros-tral end of the nervous system, they also becamemore vulnerable to injury.

The soma, or body wall, includes all of the structures derivedfrom the embryonic ectoderm, such as the epidermis of theskin and the CNS. The mesodermal connective tissues of thesoma include the dermis of the skin, skeletal muscle, bone,and the outer lining of the body cavity (i.e., parietal pleuraand peritoneum). The nervous system innervates all somaticstructures as well as the internal structures making up the vis-cera. The viscera includes the great vessels derived from the in-termediate mesoderm, the urinary system, and the gonadalstructures; it also includes the inner lining of the body cavi-ties, such as the visceral pleura and peritoneum, and themesodermal tissues that surround the endoderm-lined gutand its derivative organs (e.g., lungs, liver, pancreas).

There are both somatic and visceral nerves. The somaticnerves innervate the skeletal muscles and the smooth muscleand glands of skin and body wall. The visceral nerves supplythe visceral organs of the body, transmitting informationthrough the autonomic nerves in the PNS to control the smoothmuscle and cardiac muscle as well as the glands of the visceralorgans.

Segmental OrganizationThe early pattern of segmental development is presented as aframework for understanding the nervous system. Althoughthe early muscular, skeletal, vascular, and excretory systemsand the nerves that supply the somatic and visceral structureshave the same segmental pattern, it is the nervous system thatmost clearly retains this organization in postnatal life. De-velopmentally, the basic organizational pattern of the body isthat of a longitudinal series of segments, each repeating thesame fundamental pattern. The CNS and its associated periph-eral nerves consist of approximately 43 segments, 33 of whichform the spinal cord and spinal nerves, and 10 of which formthe brain and its cranial nerves.

The basic pattern of the CNS is that seen in the spinal cord—a central cavity surrounded by inner core of gray matter and asuperficial layer of white matter (Fig. 36-9). The brain retainsthis organization, but it also contains additional regions ofgray matter that are not evident in the spinal cord. The graymatter is functionally divided into longitudinal columns ofnerve cell bodies called the cell columns. The superficial whitematter region contains the longitudinal tract systems of theCNS. The dorsal half of the gray matter is called the dorsal horn.


Neural tube

Ectoderm

Notochord

Mesoderm

Endoderm

Neural crest

■ FIGURE 36-8 ■ Transverse section of a 22–23-day-old embryoshowing the ectoderm, mesoderm, endoderm, neural crest cells,notocord, and neural tube. During development, the neural tubedevelops into the CNS and the notocord becomes the foundationupon which the vertebral column develops. The neural crest cellsbecome the progenitors of the neurons and supporting cells of theperipheral nervous system.

KEY CONCEPTS

THE DEVELOPMENTAL ORGANIZATION OF THE NERVOUS SYSTEM

■ On cross section, the embryonic neural tube de-velops into a central canal surrounded by graymatter, or cellular portion (cell columns), and white matter, or tract system of the central nervous system (CNS).

■ As the nervous system develops, it becomes seg-mented, with a repeating pattern of afferent neuronaxons forming the dorsal roots of each succeedingsegmental nerve and the exiting efferent neuronsforming the ventral roots of each succeedingsegmental nerve.

■ The nerve cells in the gray matter are arranged lon-gitudinally in cell columns, with afferent sensoryneurons located in the dorsal columns and efferentmotor neurons located in the ventral columns.

■ The axons of the cell column neurons project outinto the white matter of the CNS, forming thelongitudinal tract systems.

Cortex ofgray matter

Inner gray matter

Outer white matter

Gray matter

Central cavity

CerebrumCerebellum

Region of cerebellum

Central cavity

Inner gray matter

Outer white matter

Gray matter

Brain stem

Central cavityOuter white matterInner gray matter

Spinal cord

■ FIGURE 36-9 ■ Segmental organization of gray and white mat-ter in the CNS (highly simplified). From top to bottom, the dia-grams represent cross-sections at the levels of cerebellum, brainstem, and spinal cord. In each section, the dorsal aspect is on top.In general, white matter lies external to gray matter; however, col-lections of gray matter migrate externally into the white matter inthe developing brain (see arrows). The cerebrum resembles the cere-bellum in its external cortex of gray matter. (Marieb E.N. [1995].Human anatomy and physiology. [3rd edition, p. 383]. Redwood City,CA. The Benjamin/Cummings Publishing Company)

ing two axon-like processes—one that ends in a peripheral re-ceptor and the other that enters the central neural segment. Theaxon-like process that enters the central neural segment com-municates with a neuron called an input association (IA) neuron.The paired ventral roots of each segment are bundles of axonsthat provide efferent output to effector sites such as the musclesand glandular cells of the body segment.

Cell ColumnsThe organizational structure of the nervous system can be bestexplained and simplified as a pattern in which functionally spe-cific PNS and CNS neurons are repeated as parallel cell columnsrunning lengthwise along the nervous system. In this organiza-tional pattern, afferent neurons, dorsal horn cells, and ventralhorn cells are organized as a bilateral series of 11 cell columns.

The cell columns on each side can be further grouped ac-cording to their location in the PNS: four in the dorsal gangliathat contain sensory neurons; four in the dorsal horn contain-ing sensory IA neurons; and three in the ventral horn that con-tain motoneurons (Fig. 36-11). Each column of dorsal rootganglia projects to its particular column of IA neurons in thedorsal horn. The IA neurons distribute afferent information tolocal reflex circuitry and to more rostral and elaborate segmentsof the CNS. The ventral horns contain output association (OA)neurons and lower motoneurons, which project to the effectormuscles. The afferent and efferent cell columns of the PNS andCNS, their projections, and the type of information they trans-mit are summarized in Table 36-1.

Between the IA neurons and the OA neurons are networksof small internuncial neurons arranged in complex circuits.Internuncial neurons provide the discreteness, appropriate-ness, and intelligence of responses to stimuli. Most of the bil-lions of CNS cells in the spinal cord and brain gray matter areinternuncial neurons.

Dorsal Horn Cell Columns. Four columns of afferent (sen-sory) neurons in the dorsal root ganglia directly innervate four


GVIASVIAGSIASSIA

Neurons ofinput associationcell columns

Dorsal horn

Lateral gray horn

Dorsalroot ganglion

Spinal ormixed nerve

GVASVAGSASSA

GVESVEGSE

GVE

SVE

GSE

Neuronsofoutputcell columns

Ventral root

■ FIGURE 36-11 ■ Cell columns ofthe central nervous system. The cellcolumns in the dorsal horn containinput association (IA) neurons forthe general visceral afferent (GVA),special visceral afferent (SVA), spe-cial sensory afferent (SSA), and gen-eral somatic afferent (GSA) neuronswith cell bodies in the dorsal rootganglion. The cell columns in theventral horn contain the general vis-ceral efferent (GVE), pharyngeal ef-ferent (PE), and general somite effer-ent (GSE) neurons and their outputassociation (OA) neurons.

The ventral portion, or ventral horn, contains efferent neuronsthat communicate by way of the ventral roots with effector cellsof the body segment. Many CNS neurons develop axons thatgrow longitudinally as tract systems that communicate be-tween neighboring and distal segments of the neural tube.

Each segment of the CNS is accompanied by bilateral pairsof bundled nerve fibers, or roots, a ventral pair and a dorsal pair(Fig. 36-10). The paired dorsal roots connect a pair of dorsalroot ganglia and their corresponding CNS segment. The dorsalroot ganglia contain many afferent nerve cell bodies, each hav-


The Segmental Nerves and Their ComponentsTABLE 36-1

1. ForebrainI. Olfactory

2. II. Optic nerve

3. MidbrainV. Trigeminal (V1) ophthalmic

division

III. Oculomotor

4. PonsV. Trigeminal (V2) maxillary

division

V. Trigeminal (V3) mandibulardivision

IV. Trochlear

5. Caudal PonsVIII. Vestibular, cochlear

(vestibulocochlear)VII. Facial nerve, intermedius

portion

Facial nerve

VI. Abducens

6. Middle MedullaIX. Glossopharyngeal

7,8,9,10. Caudal MedullaX. Vagus

XIII. Hypoglossal

Spinal SegmentsC1–C4 Upper Cervical

XI. Spinal accessory nerveSpinal nerves

Receptors in olfactory mucosa

Optic nerve and retina (part of brain system,not a peripheral nerve)

Muscles: upper face: forehead, upper lidSkin, subcutaneous tissue; conjunctiva;

frontal/ethmoid sinusesIris sphincterCiliary muscleExtrinsic eye muscles

Muscles: facial expression

Skin, oral mucosa, upper teeth, hard palate,maxillary sinus

Lower jaw, muscles: masticationSkin, mucosa, teeth, anterior 2⁄3 of tongueMuscles: mastication

tensor tympanitensor veli palantini

Extrinsic eye muscle

Vestibular end organsOrgan of CortiExternal auditory meatusNasopharynxTaste buds of anterior 2⁄3 of tongueNasopharynxLacrimal, sublingual, submandibular glandsMuscles: facial expression, stapedius

Extrinsic eye muscle

Stylopharyngeus musclePosterior external earTaste buds of posterior 1⁄3 of tongueOral pharynxParotid gland; pharyngeal mucosaStylopharyngeus muscle

Muscles: pharynx, larynxPosterior external earTaste buds, pharynx, larynxVisceral organs (esophagus to midtransverse

colon, liver, pancreas, heart, lungs)Visceral organs as aboveMuscles: pharynx, larynxMuscles of tongue

Muscles: sternocleidomastoid, trapezius

Muscles of neckNeck, back of headNeck muscles

Segment and Nerve Component Innervation Function

SVA

SSAGSA

GVE

GSE

SSA

GSA

SSAGSAPE

GSE

SSA

GSAGVASVAGVE

PE

GSE

SSAGSASVAGVAGVEPE

SSAGSASVAGVA

GVEPEGSE

PE

SSAGSAGSE

Reflexes, olfaction (smell)

Facial expression, proprioceptionSomesthesiaReflexes (blink)Pupillary constrictionAccommodationEye movement, lid movement

ProprioceptionReflexes (sneeze), somesthesia

Proprioception, jaw jerkReflexes, somesthesiaMastication: speechProtects ear from loud soundTenses soft palateMoves eye down and in

Reflexes, sense of head positionReflexes, hearingSomesthesiaGag reflex: sensationReflexes: gustation (taste)Mucous secretion, reflexesLacrimation, salivationFacial expressionProtects ear from loud soundsLateral eye deviation

ProprioceptionSomesthesiaGustation (taste)Gag reflex: sensationSalivary reflex: mucous secretionAssists swallowing

ProprioceptionSomesthesiaReflexes, gustationReflexes, sensation

Parasympathetic efferentSwallowing, phonation, emesisTongue movement, reflexes

Head, shoulder movement

Proprioception, DTRsSomesthesiaHead, shoulder movement

(continued)

corresponding columns of SIA neurons in the dorsal horn.These columns are categorized as special and general affer-ents: special somatic afferent (SSA), general somatic afferent(GSA), special visceral afferent (SVA), and general visceral af-ferent (GVA).

The SSA fibers are concerned with internal sensory infor-mation such as joint and tendon sensation (i.e., propriocep-tion). Neurons in the special sensory IA cell columns relaytheir information to local reflexes concerned with posture andmovement. These neurons also relay information to the cere-bellum, contributing to coordination of movement, and to theforebrain, contributing to experience. Afferents innervatingthe vestibular system of the inner ear also belong to the spe-cial somatic afferent category.

The GSA neurons innervate the skin and other somaticstructures, responding to stimuli such as those that producepressure or pain. General sensory IA column neurons relay in-formation to protective and other local reflex circuits and pro-ject the information to the forebrain, where it is perceived aspainful, warm, cold, and the like.

The SVAs innervate specialized gut-related receptors, such asthe taste buds and receptors of the olfactory mucosa. Their cen-tral processes communicate with special visceral IA columnneurons that project to reflex circuits producing salivation,chewing, swallowing, and other responses. Forebrain projec-tion fibers from these association cells provide sensations oftaste (i.e., gustation) and smell (i.e., olfaction).

GVA neurons innervate visceral structures such as the gas-trointestinal tract, urinary bladder, and heart and great vessels;they project to the general visceral IA column, which relays in-formation to vital reflex circuits and sends information to the

forebrain regarding visceral sensations such as stomach fullnessand bladder pressure.

Ventral Horn Cell Columns. The ventral horn contains threelongitudinal cell columns: general visceral efferent (GVE),pharyngeal efferent (PE), and general somatic efferent (GSE)(Fig. 36-11). The efferent neurons for the OA in the ventralhorn originate in brain centers (motor cortex and autonomicnervous system centers) that control skeletal muscle and vis-ceral function. Each of these cell columns contains OA and ef-ferent neurons. The OA neurons coordinate and integrate thefunction of the efferent motoneurons of its column.

GVE neurons transmit the efferent output of the autonomicnervous system and are called preganglionic neurons. These neu-rons are structurally and functionally divided between eitherthe sympathetic or the parasympathetic nervous systems (dis-cussed later in this chapter). Their axons project through thesegmental ventral roots to innervate smooth and cardiac mus-cle and glandular cells of the body, most of which are in the vis-cera. In the viscera, three additional cell columns are present oneach side of the body. These become the postganglionic neu-rons of the autonomic nervous system. In the sympathetic ner-vous system, the columns are represented by the paravertebralor sympathetic chain ganglia and the prevertebral series of gan-glia (e.g., celiac ganglia) associated with the dorsal aorta. Forthe parasympathetic nervous system, these become the entericplexus in the wall of the gut-derived organs and a series of gan-glia in the head.

The PE neurons innervate the muscles of mastication, facialexpression, and muscles of the pharynx and larynx. PE neuronsalso innervate the muscles responsible for moving the head.


The Segmental Nerves and Their Components (Continued)TABLE 36-1

C5–C8 Lower Cervical

T1–L2 Thoracic, Upper Lumbar

L2–S1 Lower Lumbar, Upper Sacral

S2–S4 Lower Sacral

S5–Co2 Lower Sacral, Coccygeal

Upper limb musclesUpper limbsUpper limb muscles

Muscles: trunk, abdominal wallTrunk, abdominal wallAll of visceraAll of viscera

Muscles: trunk, abdominal wall, back

Lower limb musclesLower trunk, limbs, backMuscles: trunk, lower limbs, back

Muscles: pelvis, perineumPelvis, genitaliaHindgut, bladder, uterusHindgut, visceral organs

Perineal musclesLower sacrum, anusPerineal muscles

Segment and Nerve Component Innervation Function

SSAGSAGSE

SSAGSAGVAGVE

GSE

SSAGSAGSE

SSAGSAGVAGVE

SSAGSAGSE

Proprioception, DTRsReflexes, somesthesiaMovement, posture

ProprioceptionReflexes, somesthesiaReflexes and sensationSympathetic reflexes, vasomotor

control, sweating, piloerectionMovement, posture, respiration

Proprioception, DTRsReflexes, somesthesiaMovement, posture

ProprioceptionReflexes, somesthesiaReflexes, sensationVisceral reflexes, defecation,

urination, erection

ProprioceptionReflexes, somesthesiaReflexes, posture

Afferent (sensory) components: SSA, special somatic afferent; GSA, general somatic afferent; SVA, special visceral afferent; GVA, general visceral afferent.

Efferent (motor) components: GVE, general visceral efferent (autonomic nervous system); PE, pharyngeal efferent; GSE, general somatic efferent; DTRs, deep tendon reflexes.

The GSE neurons supply skeletal muscles of the body andhead, including those of the body, limbs, tongue, and extrinsiceye muscles. These efferent neurons transmit the commands ofthe CNS to peripheral effectors, the skeletal muscles. They arethe “final common pathway neurons” in the sequence lead-ing to motor activity. They often are called lower motoneurons(LMNs) because they are under the control of higher levels of theCNS, including precise control by upper motoneurons (UMNs).

Longitudinal TractsThe gray matter of the cell columns in the CNS is surroundedby bundles of myelinated axons (i.e., white matter) and un-myelinated axons that travel longitudinally along the lengthof the neural axis. This white matter can be divided into threelayers: an inner, a middle, and an outer layer (Fig. 36-12). Theinner layer contains short fibers that project for a maximum ofapproximately five segments before re-entering the gray mat-ter. The middle layer projects to six or more segments. Theinner and middle layer fibers have many branches, or collat-erals, that enter the gray matter of intervening segments. Theouter layer contains large-diameter axons that that can travelthe entire length of the nervous system (Table 36-2). Supra-segmental is a term that refers to higher levels of the CNS, such

as the brain stem and cerebrum and structures above a givenCNS segment. The middle and outer layer fibers have supra-segmental projections.

The longitudinal layers are arranged in bundles, or fibertracts, that contain axons that have the same destination, ori-gin, and function (Fig. 36-13). These longitudinal tracts arenamed systematically to reflect their origin and destination; theorigin is named first, and the destination is named second. Forexample, the spinothalamic tract originates in the spinal cordand terminates in the thalamus. The corticospinal tract origi-nates in the cerebral cortex and ends in the spinal cord.

The Inner Layer. The inner layer of white matter contains theaxons of neurons that connect neighboring segments of thenervous system. Axons of this layer permit the pool of mo-toneurons of several segments to work together as a functionalunit. They also allow the afferent neurons of one segment totrigger reflexes that activate motor units in neighboring and inthe same segments. In terms of evolution, this is the oldest ofthe three layers, and it is sometimes called the archilayer. It is the first of the longitudinal layers to become functional, andits circuitry may be limited to reflex types of movements, in-cluding reflex movements of the fetus (i.e., quickening) thatbegin during the fifth month of intrauterine life.

The archilayer of the white matter differs from the other twolayers in one important aspect. Many neurons in the embryonicgray matter migrate out into this layer, resulting in a rich mix-ture of neurons and local fibers called the reticular formation.The circuitry of most reflexes is contained in the reticular for-mation. In the brain stem, the reticular formation becomesquite large and contains major portions of vital reflexes, suchas those controlling respiration, cardiovascular function, swal-lowing, and vomiting. A functional system called the reticularactivating system operates in the lateral portions of the reticularformation of the medulla, pons, and especially the midbrain.Information converging from all sensory modalities, includingthose of the somesthetic, auditory, visual, and visceral afferentnerves, bombards the neurons of this system.

The reticular activating system has descending and ascend-ing portions. The descending portion communicates with allspinal segmental levels through middle layer reticulospinaltracts and serves to facilitate many cord-level reflexes. For ex-ample, it speeds reaction time and stabilizes postural reflexes.The ascending portion accelerates brain activity, particularlythalamic and cortical activity. This is reflected by the appearanceof awake brain-wave patterns. Sudden stimuli result in pro-tective and attentive postures and cause increased awareness.


Gray matter(dorsal horn)

Archilayerwith reticularformation

Paleolayer

Neolayer

Tract fiberssynapsingon lower motorneurons

■ FIGURE 36-12 ■ The three concentric subdivisions of the tractsystems of the white matter. Migration of neurons into the archi-layer converts it into the reticular formation of the white matter.

Characteristics of the Concentric Subdivisions of the LongitudinalTracts in the White Matter of the Central Nervous System

TABLE 36-2

Segmental spanNumber of synapses

Conduction velocityExamples of functional

systems

Characteristics Archilayer Tracts Paleolayer Tracts Neolayer Tracts

Intersegmental (<5 segments)Multisynaptic

Very slowFlexor withdrawal reflex

circuitry

SuprasegmentalMonosynaptic with target

structuresFastestCorticospinal tracts

Suprasegmental (≥5 segments)Multisynaptic but fewer than

archilayer tractsFastSpinothalamic tracts

The Middle Layer. The middle layer of the white matter con-tains most of the major fiber tract systems required for sensa-tion and movement. It contains the ascending spinoreticularand spinothalamic tracts. This layer consists of larger-diameterand longer suprasegmental fibers, which ascend to the brainstem and are largely functional at birth. In terms of evolution-ary development, these tracts are quite old, and this layer issometimes called the paleolayer. It facilitates many primitivefunctions, such as the auditory startle reflex, which occurs in re-sponse to loud noises. This reflex consists of turning the headand body toward the sound, dilating the pupils of the eyes,catching of the breath, and quickening of the pulse.

The Outer Layer. The outer layer of the tract systems is thenewest of the three layers with respect to evolutionary devel-opment, and it is sometimes called the neolayer. It becomesfunctional approximately the second year of life, and it in-cludes the pathways needed for bladder training. Myelinationof these suprasegmental tracts, which include many pathwaysrequired for delicate and highly coordinated skills, is not com-plete until approximately the fifth year of life. This includes thedevelopment of tracts needed for fine manipulative skills, suchas the finger-thumb coordination required for using tools andthe toe movements needed for acrobatics. Neolayer tracts arethe most recently evolved systems and, being more superficialon the brain and spinal cord, are the most vulnerable to injury.

Collateral Communication Pathways. Axons in the archi-layer and paleolayer characteristically possess many collateralbranches that move into the gray cell columns or synapse withfibers of the reticular formation as the axon passes each suc-ceeding CNS segment. Should a major axon be destroyed atsome point along its course, these collaterals provide multi-synaptic alternative pathways that bypass the local damage.Damage usually is followed by slow return of function, pre-sumably through the collateral connections.

Neolayer tracts do not possess these collaterals but insteadproject mainly to the target neurons with which they commu-nicate. When neolayer tracts are damaged, the paleolayer andarchilayer tracts often remain functional, and rehabilitationmethods can result in effective use of the older systems. Deli-cacy and refinement may be lost, but basic function remains.For example, when the corticospinal system, an important neo-layer system that permits the fine manipulative control re-quired for writing, is damaged, the remaining paleolayer sys-tems, if intact, permit the grasping and holding of objects. Thehand can still be used to perform its basic function, but the in-dividual manipulation of the fingers is permanently lost.


Posterior median sulcus

Central canalLateralcorticospinal tract

Rubrospinal tract

Medialreticulospinal tract

Lateralreticulospinal tract

Vestibulospinal tractTectospinaltract

Anterior corticospinal tract

Anteriormedian fissure

Anteriorspinothalamic tract

Spinal nerve

Lateralspinothalamic tract

Anteriorspinocerebellar tract

Posteriorspinocerebellar tract

Posterior columns

Sensory (ascending) tractsMotor (descending) tracts

■ FIGURE 36-13 ■ Transverse sec-tion of the spinal cord showing se-lected sensory and motor tracts.The tracts are bilateral but are onlyindicated on one half of the cord.

In summary, the nervous system can be divided into twoparts: the CNS, which consists of the brain and spinal cord,and the PNS, which contains the neurons and neuronalprocesses that leave the CNS and innervate skeletal musclesand visceral structures of the body. The brain stem and spinalcord are subdivided into the dorsal horn, which containsneurons that receive and process incoming or afferent infor-mation, and the ventral horn, which contains efferent moto-neurons that handle the final stages of output processing.

Throughout life, the organization of the nervous systemretains many patterns established during early embryonic life.Each of the 43 or more body segments is connected to corre-sponding CNS or neural tube segments by segmental afferentand efferent neurons. Afferent or sensory neuronal processesthat carry afferent or sensory information enter the CNSthrough the dorsal root ganglia and the dorsal roots. Afferentneurons of the dorsal root ganglia are of four types: GSA, SSA,GVA, and SVA. Each of these afferent neurons synapses withits appropriate IA neurons in the cell columns of the dorsalhorn. There are three cells columns in the ventral horn. TheOA neurons in these columns synapse with ventral hornmotoneurons that exit the CNS in the ventral roots. GSE

THE SPINAL CORD AND BRAIN

The Spinal CordIn the adult, the spinal cord is found in the upper two thirds ofthe spinal canal of the vertebral column (Fig. 36-14A). It ex-tends from the foramen magnum at the base of the skull to acone-shaped termination, the conus medullaris, usually at thelevel of the first or second lumbar vertebra (L1 or L2) in theadult. The dorsal and ventral roots of the more caudal portionsof the cord elongate during development and angle downwardfrom the cord, forming what is called the cauda equina (fromthe Latin for “horse’s tail”). The filum terminale, which is com-posed of non-neural tissues and the pia mater, continues cau-dally and attaches to the second sacral vertebra (S2).

The spinal cord is somewhat oval on transverse section.Internally, the gray matter has the appearance of a butterfly orthe letter “H” on cross section (Fig. 36-14B). The extensions of the gray matter that form the letter “H” are called the horns.Those that extend posteriorly are called the dorsal horns, andthose that extend anteriorly are called the ventral horns. Thecentral portion of the cord, which connects the dorsal andventral horns, is called the intermediate gray matter. The inter-


neurons are LMNs that innervate skeletal muscles; PE neuronsinnervate pharyngeal muscles; and GVE neurons innervate vis-ceral structures. This pattern of afferent and efferent neurons,which in general is repeated in each segment of the body,forms parallel cell columns running lengthwise through theCNS and PNS.

Longitudinal communication between CNS segments isprovided by tracts that are arranged in three layers: an inner,middle, and outer layer. The inner layer of white matter con-tains the axons of neurons that connect neighboring seg-ments of the nervous system. It contains a mix of nerve cellsand axons called the reticular formation and is the site ofmany important spinal cord and brain stem reflex circuits.The middle layer tracts provide the longitudinal communica-tion between more distant segments of the nervous system; itcontains most of the major fiber tract systems required forsensation and movement. The recently evolved outer or neo-layer systems, which become functional during infancy andchildhood, provide the means for very delicate and discrimi-native function. The outer position of the neolayer tracts andtheir lack of collateral and redundant pathways make themthe most vulnerable to injury.

Cervical plexus(C1–C5)

Posterior view

Brachial plexus(C5–T1)

Lumbar plexus(L1–L4)

Sacral plexus(L4–S5)

Sciatic nerve

Cervicalnerves(8 pairs)

Thoracicnerves(12 pairs)

Lumbarnerves(5 pairs)

Sacralnerves(5 pairs)

Coccygeal nerves(1 pair)

T12

T1C8

L1

L5

S1

S5

C1

Thoracic

Lumbar

Sacral

White matter

CervicalVentral horn of gray matter

Dorsal horn of gray matter

Lateral horn of gray matter

■ FIGURE 36-14 ■ (A) Dorsal view of the spinal cord including portions of the major spinal nerves andsome of the components of the major nerve plexuses. (B) Cross-sectional views of the spinal cord, show-ing regional variations in gray matter and increasing white matter as the cord ascends.

A

B

mediate gray matter surrounds the central canal. In the thoracicarea, the small, slender projections that emerge from the inter-mediate gray matter are called the intermediolateral columns ofthe horns. These columns contain the visceral OA neurons andthe efferent neurons of the sympathetic nervous system.

The gray matter is proportional to the amount of tissue in-nervated by a given segment of the cord (Fig. 36-14B). Largeramounts of gray matter are present in the lower lumbar andupper sacral segments, which supply the lower extremities, andin the fifth cervical segment to the first thoracic segment, whichsupply the upper limbs. The white matter in the spinal cordalso increases progressively toward the brain because ever moreascending fibers are added and the number of descendingaxons is greater.

The spinal cord and the dorsal and ventral roots are coveredby a connective tissue sheath, the pia mater, which also con-tains the blood vessels that supply the white and gray matter ofthe cord (Fig. 36-15). On the lateral sides of the spinal cord, ex-tensions of the pia mater, the denticulate ligaments, attach thesides of the spinal cord to the bony walls of the spinal canal.Thus, the cord is suspended by both the denticulate ligamentsand the segmental nerves. A fat- and vessel-filled epidural spaceintervenes between the spinal dura mater and the inner wall ofthe spinal canal. Each vertebral body has two pedicles that ex-tend posteriorly and support the laterally oriented transverseprocesses of the neural laminae, which arch medially and fuseto continue as the spinal processes.

The spaces between the vertebral bodies are filled with fibro-cartilaginous discs and stabilized with tough ligaments. A gap,the intervertebral foramen, occurs between each two succeed-ing pedicles, allowing for the exit of the segmental nerves andpassage of blood vessels. The spinal cord lives in the protectiveconfines of this series of concentric flexible tissue and bodysheaths. Supporting structures of the spinal cord are discussedfurther in Chapter 37.

Early in fetal life, the spinal cord extends the entire length ofthe vertebral column and the spinal nerves exit through the in-tervertebral foramina (openings) near their level of origin.Because the vertebral column and spinal dura grow faster than

the spinal cord, a disparity develops between each succeedingcord segment and the exit of its dorsal and ventral nerve rootsthrough the corresponding intervertebral foramina. In the new-born, the cord terminates at the level of L2 or L3. In the adult,the cord usually terminates in the inferior border of L1, and thearachnoid and its enclosed subarachnoid space, which is filledwith CSF, do not close down on the filum terminale until theyreach the level of S2 (Fig. 36-16). This results in the formationof a pocket of CSF, the dural cisterna spinalis, which extendsfrom approximately L2 to S2. Because this area contains anabundant supply of CSF and the spinal cord does not extendthis far, the area often is used for sampling the CSF. A proce-dure called a spinal tap, or puncture, can be done by inserting aspecial needle into the dural sac at L3 or L4. The spinal roots,which are covered with pia mater, are in little danger of traumafrom the needle used for this purpose.

Spinal NervesThe peripheral nerves that carry information to and from thespinal cord are called spinal nerves. There are 32 or more pairsof spinal nerves (i.e., 8 cervical, 12 thoracic, 5 lumbar, 5 sacral,and 2 or more coccygeal); each pair is named for the segmentof the spinal cord from which it exits. Because the first cervicalspinal nerve exits the spinal cord just above the first cervical ver-tebra (C1), the nerve is given the number of the bony vertebrajust below it. However, the numbering is changed for all lowerlevels. An extra cervical nerve, the C8 nerve, exits above the T1vertebra, and each subsequent nerve is numbered for the ver-tebra just above its point of exit (Fig. 36-17).

Each spinal cord segment communicates with its corre-sponding body segment through the paired segmental spinalnerves. Each spinal nerve, accompanied by the blood vesselssupplying the spinal cord, enters the spinal canal through anintervertebral foramen, where it divides into two branches, or


Spinal cordDura mater

Arachnoid

Pia mater

Ventral root

Dorsal root

Dorsal rootganglion

Paired spinal nerves

Vertebrae

■ FIGURE 36-15 ■ Spinal cord and meninges.

roots. One branch enters the dorsolateral surface of the cord(i.e., dorsal root), carrying the axons of afferent neurons intothe CNS. The other branch leaves the ventrolateral surface ofthe cord (i.e., ventral root), carrying the axons of efferent neu-rons into the periphery. These two branches or roots fuse atthe intervertebral foramen, forming the mixed spinal nerve—“mixed” because it has both afferent and efferent axons.

After emerging from the vertebral column, the spinal nervedivides into two branches or rami (singular, ramus): a smalldorsal primary ramus and a larger ventral primary ramus (Fig. 36-18). The thoracic and upper lumbar spinal nerves alsolead to a third branch, the ramus communicans, which con-tains sympathetic axons supplying the blood vessels, the geni-tourinary system, and the gastrointestinal system. The dorsalramus contains sensory fibers from the skin and motor fibersto muscles of the back. The anterior primary ramus containsmotor fibers that innervate the skeletal muscles of the anteriorbody wall and the legs and arms.

Spinal nerves do not go directly to skin and muscle fibers;instead, they form complicated nerve networks called plexuses(Fig. 36-14A). A plexus is a site of intermixing nerve branches.Many spinal nerves enter a plexus and connect with other spi-nal nerves before exiting from the plexus. Nerves emergingfrom a plexus form progressively smaller branches that supplythe skin and muscles of the various parts of the body. The PNScontains four major plexuses: the cervical plexus, the brachialplexus, the lumbar plexus, and the sacral plexus.

The BrainThe brain is divided into three regions, the hindbrain, the mid-brain, and the forebrain (Fig. 36-19A). The hindbrain includesthe medulla oblongata, the pons, and its dorsal outgrowth, thecerebellum (see Chapter 38). Midbrain structures include twopairs of dorsal enlargements: the superior and inferior colliculi.The forebrain, which consists of two hemispheres and is cov-ered by the cerebral cortex, contains central masses of gray mat-ter, the basal ganglia (discussed in Chapter 38), and the rostralend of the neural tube, the diencephalon with its adult deriva-tives—the thalamus and hypothalamus.

An important concept is that the more rostral, recently de-veloped parts of neural tube gain dominance or control overregions and functions at lower levels. They do not replace themore ancient circuitry but merely dominate it. After damage to


Pia mater

Subarachnoid space

Dorsal root

Arachnoid

Dura mater

Dorsal primary ramus

Ventral primary ramus

Ramicommunicans

Ventral root

Third thoracicvertebra

■ FIGURE 36-18 ■ Cross-section of vertebral column at the levelof the third thoracic vertebra, showing the meninges, the spinalcord, and the origin of a spinal nerve and its branches or rami.

the more vulnerable parts of the forebrain, as occurs with braindeath, a brain stem-controlled organism remains that is capa-ble of breathing and may survive if the environmental temper-ature is regulated and nutrition and other aspects of care areprovided. However, all aspects of intellectual function, experi-ence, perception, and memory usually are permanently lost.The organization of content in this section moves from themore ancient circuitry of the hindbrain to the more dominantand recently developed structures of the forebrain.

HindbrainThe term brain stem often is used to include the hindbrain,pons, and the midbrain. These regions of the neural tubehave the organization of spinal cord segments, except thatmore of the longitudinal cell columns are present, reflectingthe increased complexity of the cranial segmental nerves. Inthe brain stem, the structure and function of the reticular for-mation have been greatly expanded. In the pons and medulla,the reticular formation contains networks controlling basicbreathing, eating, and locomotion functions. Higher-levelintegration of these functions occurs in the midbrain. The retic-ular formation is surrounded on the outside by the long tractsystems that connect the forebrain with lower parts of theCNS.

Medulla. The medulla oblongata represents the caudal five seg-ments of the brain part of the neural tube; the cranial nervebranches entering and leaving it have functions similar to thespinal segmental nerves. Although the ventral horn areas inthe medulla are quite small, the dorsal horn areas are enlarged,


Parietal lobe

Parieto-occipitalfissure

Occipitallobe

Transversefissure

Central fissure(Rolando)

Frontal lobe

Lateral fissure(Sylvius) Temporal

lobe

Diencephalon

Cerebral aqueduct

Midbrain

Brainstem

Corpuscallosum

Septumpellucidum

Frontallobe

Interventricularforamen

Anteriorcommissure

MidbrainPons

Medullaoblongata

Spinal cord

Central canalCerebellum

Fourthventricle

Cerebralaqueduct

Pinealbody

Occipitallobe

Thirdventricle

■ FIGURE 36-19 ■ (A) Midsagittal section of the brain showing the structures of the forebrain, midbrain,and hindbrain. (B) Lateral view of the cerebral hemispheres. (C) Diencephalon, brain stem, and the cere-bral aqueduct connecting the 3rd and 4th ventricles.

processing a large amount of the information pouring throughthe cranial nerves. Cranial nerves XII (hypoglossal), X (vagus),and (IX) glossopharyngeal have their origin in the medulla(see Table 36-1).

Pons. The pons, which develops from the fifth neural tube seg-ment, is located between the medulla oblongata and the mid-brain. Dorsally, it forms part of the anterior wall of the fourthventricle (Fig. 36-19B).

As the name implies (pons = bridge), the pons is composedchiefly of conduction fibers. The enlarged area on the ventralsurface of the pons contains the pontine nuclei, which receiveinformation from all parts of the cerebral cortex. The axons ofthese neurons form a massive bundle that swings around thelateral side of the fourth ventricle to enter the cerebellum. Inthe pons, the reticular formation is large and contains the cir-cuitry for masticating food and manipulating the jaws duringspeech. Cranial nerves VIII, VII, and VI have their origin in thepons (see Table 36-1).

MidbrainThe midbrain develops from the fourth segment of the neuraltube, and its organization is similar to that of a spinal segment.The central canal is re-established as the cerebral aqueduct,connecting the fourth ventricle with the third ventricle (see Fig. 36-19B).

Two prominent bundles of nerve fibers, the cerebral pedun-cles, pass along the ventral surface of the midbrain. Thesefibers include the corticospinal tracts and are the main motorpathways between the forebrain and the pons. On the dorsal

The thalamus also plays a role in relaying critical informa-tion regarding motor activities to and from selected areas ofthe motor cortex. Two neuronal circuits are significant in thisregard. One is the pathway from the cerebral cortex to thepons and cerebellum and then, by way of the thalamus, backto the motor cortex. The second is the feedback circuit thattravels from the cortex to the basal ganglia, then to the thala-mus, and from the thalamus back to the cortex. The subthal-amus also contains movement control systems related to thebasal ganglia.

Through its connections with the ascending reticular acti-vating system, the thalamus processes neural influences that arebasic to cortical excitatory rhythms (i.e., those recorded on theelectroencephalogram), to essential sleep-wakefulness cycles,and to the process of attending to stimuli. Besides their corticalconnections, the thalamic nuclei have connections with eachother and with neighboring nonthalamic brain structures suchas the limbic system. Through their connections with the lim-bic system, some thalamic nuclei are involved in the relationbetween stimuli and the emotional responses they evoke.

The ventral horn portion of the diencephalon is the hypo-thalamus, which borders the third ventricle and includes aventral extension, the neurohypophysis (i.e., posterior pitu-itary). The hypothalamus is the area of master-level integrationof homeostatic control of the body’s internal environment.Maintenance of blood gas concentration, water balance, foodconsumption, and major aspects of endocrine and autonomicnervous system control require hypothalamic function.

The internal capsule is a broad band of projection fibers thatlies between the thalamus medially and the basal ganglia lat-erally (see Fig. 36-20). It contains all of the fibers that connectthe cerebral cortex with deeper structures, including the basalganglia, thalamus, midbrain, pons, medulla, and spinal cord.

Cerebral Hemispheres. The two cerebral hemispheres are lat-eral outgrowths of the diencephalon. The cerebral hemispherescontain the lateral ventricles (i.e., ventricles I and II), which are


surface, four “little hills,” the superior and inferior colliculi, areareas of cortical formation. The inferior colliculus is involvedin directional turning and, to some extent, in experiencing thedirection of sound sources. The superior colliculi are essentialto the reflex mechanisms that control conjugate eye move-ments when the visual environment is surveyed. Two generalsomatic efferent cranial nerves, the oculomotor nerve, or cra-nial nerve III, and the trochlear nerve, or cranial nerve IV, exitthe midbrain (see Table 36-1).

ForebrainThe most rostral part of the brain, the forebrain consists of the telencephalon, or “end brain,” and the diencephalon, or“between brain.” The diencephalon forms the core of the fore-brain, and the telencephalon forms the cerebral hemispheres.

Diencephalon. Three of the most forward brain segments forman enlarged dorsal horn and ventral horn with a narrow, deep,enlarged central canal—the third ventricle—separating the twosides. This region is called the diencephalon. The dorsal hornpart of the diencephalon is the thalamus and subthalamus, andthe ventral horn part is the hypothalamus (Fig. 36-20). Theoptic nerve, or cranial nerve II, and retina are outgrowths ofthe diencephalon.

The thalamus consists of two large, egg-shaped masses, oneon either side of the third ventricle. The thalamus is dividedinto several major parts, and each part is divided into distinctnuclei, which are the major relay stations for information goingto and from the cerebral cortex. All sensory pathways have di-rect projections to thalamic nuclei, which convey the informa-tion to restricted areas of the sensory cortex. Coordination andintegration of peripheral sensory stimuli occur in the thalamus,along with some crude interpretation of highly emotion-ladenauditory experiences that not only occur but can be remem-bered. For example, a person can recover from a deep coma inwhich cerebral cortex activity is minimal and remember someof what was said at the bedside.

Subthalamus

Parietalcortex

Insula

Hypothalamus

Corpus callosumThalamus

Caudatenucleus

Internalcapsule

Lentiformnucleus

Amygdaloidcomplex

Thirdventricle

■ FIGURE 36-20 ■ Frontal section of the brainpassing through the third ventricle, showing thethalamus, subthalamus, hypothalamus, internalcapsule, corpus callosum, basal ganglia (caudatenucleus, lenticular nucleus), amygdaloid com-plex, insula, and parietal cortex.

connected with the third ventricle of the diencephalon by asmall opening called the interventricular foramen (i.e., foramenof Monro). Axons of the olfactory nerve, or cranial nerve I, ter-minate in the most ancient portion of the cerebrum—the ol-factory bulb, where initial processing of olfactory informationoccurs. Projection axons from the olfactory bulb relay infor-mation through the olfactory tracts to the thalamus and toother parts of the cerebral cortex (i.e., orbital cortex), where olfactory-related reflexes and olfactory experience occur.

The corpus callosum is a massive commissure, or bridge, ofmyelinated axons that connects the cerebral cortex of the twosides of the brain. Two smaller commissures, the anterior andposterior commissures, connect the two sides of the more spe-cialized regions of the cerebrum and diencephalon.

The surfaces of the hemispheres are lateral (side), medial(area between the two sides of the brain), and basal (ventral).The cerebral cortex observed laterally is the recently evolved six-layered neocortex. The surface of the hemispheres containsmany ridges and grooves. A gyrus is the ridge between twogrooves, and the groove is called a sulcus or fissure. The cerebralcortex is arbitrarily divided into lobes named after the bonesthat cover them: the frontal, parietal, temporal, and occipitallobes (Fig. 36-19C).

Frontal Lobe. The frontal lobe extends from the frontal pole tothe central sulcus (i.e., fissure) and is separated from the tem-poral lobe by the lateral sulcus. The frontal lobe can be sub-divided rostrally into the frontal pole and laterally into thesuperior, middle, and inferior gyri, which continue on theundersurface over the eyes as the orbital cortex. These areasare associated with the medial thalamic nuclei, which also arerelated to the limbic system. In terms of function, the pre-frontal cortex is thought to be involved in anticipation andprediction of consequences of behavior.

The precentral gyrus (area 4), next to the central sulcus, isthe primary motor cortex (Fig. 36-21). This area of the cortex pro-vides precise movement control for distal flexor muscles of thehands and feet and of the phonation apparatus required forspeech. Just rostral to the precentral gyrus is a region of thefrontal cortex called the premotor or motor association cortex. This

region (area 8 and rostral area 6) is involved in the planning ofcomplex learned movement patterns. The primary motor cor-tex and the association motor cortex are connected with lateralthalamic nuclei, through which they receive feedback infor-mation from the basal ganglia and cerebellum. On the medialsurface of the hemisphere, the premotor area includes a supple-mentary motor cortex involved in the control of bilateral move-ment patterns requiring great dexterity.

Parietal Lobe. The parietal lobe of the cerebrum lies behindthe central sulcus (i.e., postcentral gyrus) and above the lateralsulcus. The strip of cortex bordering the central sulcus is calledthe primary somatosensory cortex (areas 3, 1, and 2) because it re-ceives very discrete sensory information from the lateral nucleiof the thalamus. Just behind the primary sensory cortex is thesomatosensory association cortex (areas 5 and 7), which is con-nected with the thalamic nuclei and with the primary sensorycortex. This region is necessary for perceiving the meaningful-ness of integrated sensory information from various sensorysystems, especially the perception of “where” the stimulus is inspace and in relation to body parts. Localized lesions of this re-gion can result in the inability to recognize the meaningfulnessof an object (i.e., agnosia). With the person’s eyes closed, ascrewdriver can be felt and described as to shape and texture.Nevertheless, the person cannot integrate the sensory informa-tion required to identify it as a screwdriver (discussed furtherin Chapter 39).

Temporal Lobe. The temporal lobe lies below the lateral sul-cus and merges with the parietal and occipital lobes. It includesthe temporal pole and three primary gyri: the superior, middle,and inferior gyri. The primary auditory cortex (area 41) in-volves the part of the superior temporal gyrus that extends intothe lateral sulcus (see Fig. 36-21). This area is particularly im-portant in discrimination of sounds entering opposite ears. Itreceives auditory input projections by way of the inferior col-liculus of the midbrain and a ventrolateral thalamic nucleus.The more exposed part of the superior temporal gyrus involvesthe auditory association area (area 22). The recognition ofcertain sound patterns and their meaning requires the function


of this area. The remaining portion of the temporal cortex isless defined functionally but apparently is important in long-term memory recall. This is particularly true with respect to per-ception and memory of complex sensory patterns, such as geo-metric figures and faces (i.e., recognition of “what” or “who”the stimulus is). Irritation or stimulation can result in vivid hal-lucinations of long-past events.

Occipital Lobe. The occipital lobe lies posterior to the tempo-ral and parietal lobes and is only arbitrarily separated fromthem. The medial surface of the occipital lobe contains a deepsulcus extending from the limbic lobe to the occipital pole, thecalcarine sulcus, which is surrounded by the primary visual cor-tex (area 17). Stimulation of this cortex causes the experienceof bright lights (phosphenes) in the visual field. Just superiorand inferior and extending onto the lateral side of the occipitalpole is the visual association cortex (areas 18 and 19). This areais closely connected with the primary visual cortex and withcomplex nuclei of the thalamus. Integrity of the associationcortex is required for gnostic visual function, by which themeaningfulness of visual experience, including experiences ofcolor, motion, depth perception, pattern, form, and location inspace, occurs.

The neocortical areas of the parietal lobe, between the so-matosensory and the visual cortices, have a function in relat-ing the texture, or “feel,” and location of an object with its visual image. Between the auditory and visual associationareas, the parieto-occipital region is necessary for relating themeaningfulness of a sound and image to an object or person.

Limbic System. The medial aspect of the cerebrum is orga-nized into concentric bands of cortex, the limbic system (lim-bic = borders), which surrounds the connection between thelateral and third ventricles. The innermost band just above andbelow the cut surface of the corpus callosum is folded out ofsight but is an ancient, three-layered cortex ending as the hip-pocampus in the temporal lobe. Just outside the folded area isa band of transitional cortex, which includes the cingulate andthe parahippocampal gyri (Fig. 36-22). This limbic lobe hasreciprocal connections with the medial and the intralaminarnuclei of the thalamus, with the deep nuclei of the cerebrum(e.g., amygdaloid nuclei, septal nuclei), and with the hypo-thalamus. Overall, this region of the brain is involved in emo-tional experience and in the control of emotion-related be-havior. Stimulation of specific areas in this system can lead tofeelings of dread, high anxiety, or exquisite pleasure. It alsocan result in violent behaviors, including attack, defense, or ex-plosive and emotional speech.

MeningesInside the skull and vertebral column, the brain and spinalcord are loosely suspended and protected by several connectivetissue sheaths called the meninges (Fig. 36-23). The surfaces ofthe spinal cord, brain, and segmental nerves are covered with adelicate connective tissue layer called the pia mater (Latin for“delicate mother”). The surface blood vessels and those thatpenetrate the brain and spinal cord are encased in this pro-tective tissue layer. A second, very delicate, nonvascular, andwaterproof layer, called the arachnoid, encloses the entire CNS.The arachnoid layer is named for its spider web appearance.The CSF is contained in the subarachnoid space. Immediately

outside the arachnoid is a continuous sheath of strong con-nective tissue, the dura mater (i.e., “tough mother”), which pro-vides the major protection for the brain and spinal cord. Thecranial dura often splits into two layers, with the outer layerserving as the periosteum of the inner surface of the skull.

The inner layer of the dura forms two major folds. The first,a longitudinal fold called the falx cerebri, separates the cerebralhemispheres and fuses with a second transverse fold, called thetentorium cerebelli (Fig. 36-24). The tentorium cerebelli sepa-rates the anterior and middle depression in the skull (cranialfossae), which contains the cerebral hemispheres, from theposterior fossa, found interiorly and containing the brain stemand cerebellum. A semicircular gap, or incisura, is formed at themidline to permit the midbrain to pass forward from the pos-terior fossa.


Cingulate gyrus

Olfactorybulb

Mammilarybody

AmygdalaUncus

Temporal lobe

Parahippocampalgyrus

Corpus callosum Anterior nucleusof thalamus

Fornix

■ FIGURE 36-22 ■ The limbic system includes the limbic cortex(cingulated gyrus, parahippocampal gyrus, uncus) and associatedsubcortical structures (thalamus, hypothalamus, amygdala).

■ FIGURE 36-23 ■ The cranial meninges. Arachnoid villi, shownwithin the superior sagittal sinus, are one site of cerebrospinalfluid absorption into the blood.

Superior sagittal sinus

Subarachnoidspace

Subduralspace

Skin

Periosteum

Bone

Dura mater

Arachnoid

Pia mater

Falxcerebri

Arachnoid villi

Ventricular System and Cerebrospinal FluidThe ventricular system is a series of CSF-filled cavities in thebrain (Fig. 36-25). The CSF provides a supporting and pro-tective fluid in which the brain and spinal cord float. CSF helpsmaintain a constant ionic environment that serves as a me-dium for diffusion of nutrients, electrolytes, and metabolic end-products into the extracellular fluid surrounding CNS neuronsand glia. Filling the ventricles, the CSF supports the mass of thebrain. Because it fills the subarachnoid space surrounding theCNS, a physical force delivered to either the skull or spine is tosome extent diffused and cushioned.

The lining of the ventricles and central canal of the spinalcord is called the ependyma. There is a tremendous expansionof the ependyma in the roof of the lateral, third and fourth ven-tricles. The CSF is produced by tiny reddish masses of special-ized capillaries from the pia mater, called the choroid plexus, thatproject into the ventricles. CSF is an ultrafiltrate of bloodplasma, composed of 99% water with other constituents, mak-

ing it close to the composition of the brain extracellular fluid.Humans secrete approximately 500 mL of CSF each day. How-ever, only approximately 150 mL is in the ventricular system atany one time, meaning that the CSF is continuously beingabsorbed.

Once produced, the CSF flows freely through the ventricles.Three openings, or foramina, allow the CSF to pass into thesubarachnoid space. Two of these, the foramina of Luschka,are located at the lateral corners of the fourth ventricle. Thethird, the medial foramen of Magendie, is in the midline atthe caudal end of the fourth ventricle (see Fig. 36-25). Ap-proximately 30% of the CSF passes down into the subarach-noid space that surrounds the spinal cord, mainly on its dor-sal surface, and moves back up to the cranial cavity along itsventral surface.

Reabsorption of CSF into the vascular system occurs alongthe sides of the superior sagittal sinus in the anterior and mid-dle fossa. Here, the waterproof arachnoid has protuberances,the arachnoid villi, that penetrate the inner dura and venouswalls of the superior sagittal sinus. The arachnoid villi functionas one-way valves, permitting CSF outflow into the blood butnot allowing blood to pass into the arachnoid spaces.

Blood-Brain and Cerebrospinal Fluid–Brain BarriersMaintenance of a chemically stable environment is essential tothe function of the brain. In most regions of the body, extra-cellular fluid undergoes small fluctuations in pH and concen-trations of hormones, amino acids, and potassium ions duringroutine daily activities such as eating and exercising. If the brainwere to undergo such fluctuations, the result would be un-controlled neural activity because some substances such asamino acids act as neurotransmitters, and ions such as potas-sium influence the threshold for neural firing. Two barriers, theblood-brain barrier and the CSF-brain barrier, provide the meansfor maintaining the stable chemical environment of the brain.Only water, carbon dioxide, and oxygen enter the brain withrelative ease; the transport of other substances between thebrain and the blood is slow.


■ FIGURE 36-24 ■ Cranial dura mater. The skull is open to showthe falx cerebri and the tentorium cerebelli, as well as some of thecranial venous sinuses.

Choroidal plexusfourth ventricle

Foramen of Magendie

Choroidalplexus thirdventricle

Arachnoid villiSuperiorsagittal

sinus

Subarachnoidspace

Interventricularforamen

■ FIGURE 36-25 ■ The flow of cerebrospinalfluid from the time of its formation from bloodin the choroid plexuses until its return to theblood in the superior sagittal sinus. Plexuses inthe lateral ventricles are not illustrated.

Blood-Brain Barrier. The blood-brain barrier depends on theunique characteristics of the brain capillaries. The endothelialcells of brain capillaries are joined by continuous tight junc-tions. In addition, most brain capillaries are completely sur-rounded by a basement membrane and by the processes ofsupporting cells of the brain, called astrocytes (Fig. 36-26). Theblood-brain barrier permits passage of essential substanceswhile excluding unwanted materials. Reverse transport sys-tems remove materials from the brain. Large molecules suchas proteins and peptides are largely excluded from crossingthe blood-brain barrier. Acute cerebral lesions, such as traumaand infection, increase the permeability of the blood-brainbarrier and alter brain concentrations of proteins, water, andelectrolytes.

The blood-brain barrier prevents many drugs from enteringthe brain. Most highly water-soluble compounds are excludedfrom the brain, especially molecules with high ionic charge,such as many of the catecholamines. In contrast, many lipid-soluble molecules cross the lipid layers of the blood-brain bar-rier with ease. Some drugs, such as the antibiotic chloram-phenicol, are highly lipid soluble and therefore enter the brainreadily. Other medications have a low solubility in lipids andenter the brain slowly or not at all. Alcohol, nicotine, and her-oin are very lipid soluble and rapidly enter the brain. Somesubstances that enter the capillary endothelium are convertedby metabolic processes to a chemical form incapable of mov-ing into the brain.

The cerebral capillaries are much more permeable at birththan in adulthood, and the blood-brain barrier develops dur-ing the early years of life. In severely jaundiced infants, biliru-bin can cross the immature blood-brain barrier, producing ker-nicterus and brain damage (see Chapter 15). In adults, themature blood-brain barrier prevents bilirubin from enteringthe brain, and the nervous system is not affected.

Cerebrospinal Fluid–Brain Barrier. The ependymal cells cover-ing the choroid plexus are linked together by tight junctions,forming a blood-CSF barrier to diffusion of many moleculesfrom the blood plasma of choroid plexus capillaries to the CSF.Water is transported through the choroid epithelial cells by os-mosis. Oxygen and carbon dioxide move into the CSF by dif-fusion, resulting in partial pressures roughly equal to those ofplasma. The high sodium and low potassium contents of theCSF are actively regulated and kept relatively constant. Lipidsand nonpeptide hormones diffuse through the barrier rathereasily, but most large molecules, such as proteins, peptides,many antibiotics, and other medications, do not normally getthrough. Many substances such as proteins; sodium ions; anumber of micronutrients such as vitamins C, B6 (pyridoxine),and folate are actively secreted into the CSF by the choroid epithelium. Because the resultant CSF has a relatively highsodium content, the negatively charged chloride and bicar-bonate diffuse into the CSF along an ionic gradient. The cho-roid cells also generate bicarbonate from carbon dioxide in theblood. The generation of bicarbonate is important to the regu-lation of the pH of the CSF.

Mechanisms exist that facilitate the transport of other mol-ecules such as glucose without energy expenditure. Ammonia,a toxic metabolite of neuronal activity, is converted to gluta-mine by astrocytes. Glutamine moves by facilitated diffusionthrough the choroid epithelium into the plasma. This exem-plifies a major function of the CSF, that of providing a meansof removal of toxic waste products from the CNS. Because thebrain and spinal cord have no lymphatic channels, the CSFserves this function.

There are several specific areas of the brain where theblood-CSF barrier does not exist. One area is at the caudal endof the fourth ventricle, where specialized receptors for the car-bon dioxide level of the CSF influence respiratory function.Another area consists of the walls of the third ventricle, whichpermit hypothalamic neurons to monitor blood glucose lev-els. This mechanism permits hypothalamic centers to respondto these blood glucose levels, contributing to hunger and eating behaviors.


Tight junctions ofoverlapping capillaryendothelial cells

Continuousbasementmembrane

Covering ofastrocyteend feet

Astrocyteend feet

Astrocyte

■ FIGURE 36-26 ■ The three components of the blood-brain bar-rier: the astrocyte and astrocytic feet that encircle the capillary, thecapillary basement membrane, and the tight junctions that jointhe overlapping capillary endothelial cells.

In summary, in the adult, the spinal cord is in the uppertwo thirds of the spinal canal of the vertebral column. Ontransverse section, the spinal cord has an oval shape, and theinternal gray matter has the appearance of a butterfly or letter“H.” The dorsal horns contain the IA neurons and receive afferent information from dorsal root and other connectingneurons. The ventral horns contain the OA neurons and effer-ent LMNs that leave the cord by the ventral roots. Thirty-twopairs of spinal nerves (i.e., 8 cervical, 12 thoracic, 5 lumbar, 5 sacral, and 2 or more coccygeal) are present. Each paircommunicates with its corresponding body segments. Thespinal nerves and the blood vessels that supply the spinal cordenter the spinal canal through an intervertebral foramen.After entering the foramen, they divide into two branches, orroots, one of which enters the dorsolateral surface of the cord(i.e., dorsal root), carrying the axons of afferent neurons intothe CNS. The other root leaves the ventrolateral surface of thecord (i.e., ventral root), carrying the axons of efferent neuronsinto the periphery. These two roots fuse at the intervertebralforamen, forming the mixed spinal nerve.

THE AUTONOMIC NERVOUS SYSTEM

The ability to maintain homeostasis and perform the activi-ties of daily living in an ever-changing physical environmentis largely vested in the autonomic nervous system (ANS). TheANS functions at the subconscious level and is involved inregulating, adjusting, and coordinating vital visceral functionssuch as blood pressure and blood flow, body temperature,respiration, digestion, metabolism, and elimination. The ANSis strongly affected by emotional influences and is involved in many of the expressive aspects of behavior. Blushing, pal-lor, palpitations of the heart, clammy hands, and dry mouthare several emotional expressions that are mediated throughthe ANS.

As with the somatic nervous system, the ANS is repre-sented in both the CNS and the PNS. Traditionally, the ANShas been defined as a general efferent system innervatingvisceral organs. The efferent outflow from the ANS has twodivisions: the sympathetic nervous system and the parasym-pathetic nervous system. The afferent input to the ANS is pro-

vided by visceral afferent neurons, usually not considered tobe part of the ANS.

The functions of the sympathetic nervous system includemaintaining body temperature and adjusting blood flow andblood pressure to meet the changing needs of the body thatoccur with activities of daily living, such as moving from thesupine to the standing position. The sympathoadrenal systemalso can discharge as a unit when there is a critical threat tothe integrity of the individual—the so-called fight-or-flight re-sponse. During a stress situation, the heart rate accelerates; theblood pressure rises; blood flow shifts from the skin and gastro-intestinal tract to the skeletal muscles and brain; blood sugarincreases; the bronchioles and pupils dilate; the sphincters ofthe stomach and intestine and the internal sphincter of the ure-thra constrict; and the rate of secretion of exocrine glands thatare involved in digestion diminishes. Emergency situationsoften require vasoconstriction and shunting of blood awayfrom the skin and into the muscles and brain, a mechanismthat, should a wound occur, provides for a reduction in bloodflow and preservation of vital functions needed for survival.Sympathetic function often is summarized as catabolic in thatits actions predominate during periods of pronounced energyexpenditure, such as when survival is threatened.

In contrast to the sympathetic nervous system, the functionsof the parasympathetic nervous system are concerned withconservation of energy, resource replenishment and storage(i.e., anabolism), and maintenance of organ function duringperiods of minimal activity. The parasympathetic nervous sys-tem slows heart rate, stimulates gastrointestinal function andrelated glandular secretion, promotes bowel and bladder elim-ination, and contracts the pupil, protecting the retina from ex-cessive light during periods when visual function is not vital tosurvival. The two divisions of the ANS usually are viewed ashaving opposite and antagonistic actions (i.e., if one activates,the other inhibits a function). Exceptions are functions, such assweating and regulation of arteriolar blood vessel diameter,


KEY CONCEPTS

THE AUTONOMIC NERVOUS SYSTEM (ANS)

■ The ANS functions at the subconscious level and isresponsible for maintaining homeostatic functions of the body.

■ The ANS has two divisions: the sympathetic andparasympathetic systems. Although the two divi-sions function in concert, they are generally viewedas having opposite and antagonistic actions.

■ The sympathetic nervous system functions in main-taining vital functions and responding when there isa critical threat to the integrity of the individual—the “fight-or-flight” response.

■ The parasympathetic nervous system functions inconserving energy, resource replenishment, andmaintenance of organ function during periods ofminimal activity.

The brain can be divided into three regions: the hindbrain,the midbrain, and the forebrain. The hindbrain, consisting ofthe medulla oblongata, pons, and cerebellum, contains theneuronal circuits for the eating, breathing, and locomotivefunctions required for survival. Cranial nerves XII, XI, X, IX,VIII, VII, VI, and V are located in the hindbrain. The midbraincontains cranial nerves III and IV.

The forebrain is the most rostral part of the brain; it con-sists of the diencephalon and the telencephalon. The dien-cephalon forms the core of the forebrain, and telencephalonforms the cerebral hemispheres. The dorsal horn part of thediencephalon contains the thalamus and subthalamus, andthe ventral horn contains the hypothalamus. All sensory path-ways have direct projections to the thalamic nuclei, whichconvey the information to restricted parts of the sensory cor-tex. The hypothalamus functions in the homeostatic controlof the internal environment. The cerebral hemispheres are thelateral outgrowths of the diencephalon and are arbitrarily di-vided into lobes—the frontal, parietal, temporal, and occipitallobes. The prefrontal premotor area and primary motor cortexare located in the frontal lobe; the primary sensory cortex andsomatosensory association area are in the parietal cortex; theprimary auditory cortex and the auditory association area arein the temporal lobe; and the primary visual cortex and asso-ciation visual cortex are in the occipital lobe. The limbic sys-tem, which is involved in emotional experience and release ofemotional behaviors, is located in the medial aspect of thecerebrum.

The brain is enclosed and protected by the pia mater,arachnoid, and dura mater. The protective CSF in which thebrain and spinal cord float isolates them from minor andmoderate trauma. The CSF is secreted into the ventricles, circulates through the ventricular system, passes outside tosurround the brain, and is reabsorbed into the venous systemthrough the arachnoid villi. The CSF-brain barrier and theblood-brain barrier protect the brain from substances in theblood that would disrupt brain function.

that are controlled by a single division of the ANS, in this casethe sympathetic nervous system.

The sympathetic and parasympathetic nervous systems arecontinually active. The effect of this continual or basal (base-line) activity is referred to as tone. The tone of an effector organor system can be increased or decreased and usually is regulatedby a single division of the ANS. For example, vascular smoothmuscle tone is controlled by the sympathetic nervous system.Increased sympathetic activity produces local vasoconstrictionfrom increased vascular smooth muscle tone, and decreased ac-tivity results in vasodilatation caused by decreased tone. Instructures such as the sinoatrial node and atrioventricular nodeof the heart, which are innervated by both divisions of the ANS,one division predominates in controlling tone. In this case, thetonically active parasympathetic nervous system exerts a con-straining or braking effect on heart rate, and when parasympa-thetic outflow is withdrawn, similar to releasing a brake, theheart rate increases. The increase in heart rate that occurs withvagal withdrawal can be further augmented by sympatheticstimulation.

Autonomic Efferent PathwaysThe outflow of both divisions of the ANS follows a two-neuronpathway. The first motoneuron, called the preganglionic neuron,lies in the intermediolateral cell column in the ventral horn ofthe spinal cord or its equivalent location in the brain stem. Thesecond motoneuron, called the postganglionic neuron, synapseswith a preganglionic neuron in an autonomic ganglion lo-cated in the PNS. The two divisions of the ANS differ in termsof location of preganglionic cell bodies, relative length of pre-ganglionic fibers, general function, nature of peripheral re-sponses, and preganglionic and postganglionic neuromediators(Table 36-3). This two-neuron outflow pathway and the in-terneurons in the autonomic ganglia that add further modu-lation to ANS function are features distinctly different from thearrangement in somatic motor innervation.

Most visceral organs are innervated by both sympatheticand parasympathetic fibers. Exceptions include structures such

as blood vessels and sweat glands that have input from onlyone division of the ANS. The fibers of the sympathetic nervoussystem are distributed to effectors throughout the body, and asa result, sympathetic actions tend to be more diffuse than thoseof the parasympathetic nervous system, in which there is amore localized distribution of fibers. The preganglionic fibersof the sympathetic nervous system may traverse a considerabledistance and pass through several ganglia before synapsingwith postganglionic neurons, and their terminals make contactwith a large number of postganglionic fibers. In some ganglia,the ratio of preganglionic to postganglionic cells may be 1�20;because of this, the effects of sympathetic stimulation are dif-fuse. There is considerable overlap, and one ganglion cell maybe supplied by several preganglionic fibers. In contrast to thesympathetic nervous system, the parasympathetic nervous sys-tem has its postganglionic neurons located very near or in theorgan of innervation. Because the ratio of preganglionic topostganglionic communication often is 1�1, the effects of theparasympathetic nervous system are much more circumscribed.

Sympathetic Nervous SystemThe preganglionic neurons of the sympathetic nervous systemare located primarily in the thoracic and upper lumbar seg-ments (T1 to L2) of the spinal cord; thus, the sympathetic ner-vous system often is referred to as the thoracolumbar division ofthe ANS. These preganglionic neurons, which are located pri-marily in the ventral horn intermediolateral cell column, haveaxons that are largely myelinated and relatively short. The post-ganglionic neurons of the sympathetic nervous system are lo-cated in the paravertebral ganglia of the sympathetic chain thatlie on either side of the vertebral column, or in prevertebralsympathetic ganglia such as the celiac ganglia (Fig. 36-27). Inaddition to postganglionic efferent neurons, the sympatheticganglia contain neurons of the internuncial, short-axon type,similar to those associated with complex circuitry in the brainand spinal cord. Many of these inhibit and others modulatepreganglionic-to-postganglionic transmission.

The axons of the preganglionic neurons leave the spinalcord through the ventral root of the spinal nerves (T1 to L2),


Characteristics of the Sympathetic and Parasympathetic Nervous Systems

TABLE 36-3

Location of preganglionic cell bodies

Relative length of preganglionic fibers

General function

Nature of peripheral responseTransmitter between preganglionic ter-

minals and postganglionic neuronsTransmitter of postganglionic neuron

Characteristic Sympathetic Outflow Parasympathetic Outflow

T1–T12, L1 and L2

Short—to paravertebral chain of ganglia or to aorticprevertebral of ganglia

Catabolic—mobilizes resources in anticipation of chal-lenge for survival (preparation for “fight-or-flight”response)

GeneralizedACh

ACh (sweat glands and skeletal muscle vasodilatorfibers); norepinephrine (most synapses); norepineph-rine and epinephrine (secreted by adrenal gland)

Cranial nerves: III, VII (intermedius),IX, X; sacral segments 2, 3, and 4

Long—to ganglion cells near or inthe innervated organ

Anabolic—concerned with conser-vation, renewal, and storage ofresources

LocalizedACh

ACh

ACh, acetylcholine.


Sympathetic Parasympathetic

Eye

Lacrimal gland

Submandibular andsublingual glands

Parotid gland

Heart

Trachea

Lung

Liver

Gallbladder

Stomach

Small intestine

Adrenal gland

Kidney

Large intestine

Bladder

Genitalia

Greatersplanchnic

nerve

Lessersplanchnic

nerve

Ciliary ganglion

Pterygopalatineganglion

Submandibularganglion

Oticganglion

Midbrain

Medulla

Cervical

Thoracic

Lumbar

Sacral

1 = Celiac ganglion2 = Superior mesenteric ganglion3 = Inferior mesenteric ganglion

To s

kin

and

skel

etom

uscu

lar

syst

em

C = Inferior cervical ganglionB = Middle cervical ganglion

A = Superior cervical ganglion

VIIIX

X

III

1

2

B

A

C

3

■ FIGURE 36-27 ■ The autonomic nervous system. The involuntary organs are depicted with theirparasympathetic innervation (craniosacral) indicated on the right and sympathetic innervation (thora-columbar) on the left. Preganglionic fibers are solid lines; postganglionic fibers are dashed lines. For purposesof illustration, the sympathetic outflow to the skin and skeletomuscular system is shown separately (tothe far left); effectors include sweat glands, pilomotor muscles and blood vessels of the skin, and bloodvessels of the skeletal muscles and bones. (Modified from Hemer L. [1983]. The human brain and spinal cord:Functional neuroanatomy and dissection guide. New York: Springer-Verlag)

enter the ventral primary rami, and leave the spinal nervethrough white rami of the rami communicantes to reach theparavertebral ganglionic chain (Fig. 36-28). In the sympatheticchain of ganglia, preganglionic fibers may synapse with neu-rons of the ganglion it enters, pass up or down the chain andsynapse with one or more ganglia, or pass through the chainand move outward through a splanchnic nerve to terminate inone of the prevertebral ganglia (i.e., celiac, superior mesen-teric, or inferior mesenteric) that are scattered along the dor-sal aorta and its branches. The adrenal medulla, which is partof the sympathetic nervous system, contains postganglionicsympathetic neurons that secrete sympathetic neurotransmit-ters directly into the bloodstream.

Parasympathetic Nervous SystemThe preganglionic fibers of the parasympathetic nervous sys-tem, also referred to as the craniosacral division of the ANS, orig-inate in some segments of the brain stem and sacral segmentsof the spinal cord (see Fig. 36-27). The central regions of originare the midbrain, pons, medulla oblongata, and the sacral partof the spinal cord. Outflow from the midbrain passes throughthe oculomotor nerve (cranial nerve III) to supply the pupillarysphincter muscle of each eye and the ciliary muscles that con-trol lens thickness for accommodation. Caudal pontine out-

flow comes from branches of the facial nerve (cranial nerve VII)that supply the lacrimal and nasal glands. The medullary out-flow develops from cranial nerves VII, IX, and X. Fibers in theglossopharyngeal nerve (cranial nerve IX) supply the parotidsalivary glands. Approximately 75% of parasympathetic effer-ent fibers are carried in the vagus nerve (cranial nerve X). Thevagus nerve provides parasympathetic innervation for the heart,trachea, lungs, esophagus, stomach, small intestine, proximalhalf of the colon, liver, gallbladder, pancreas, kidneys, andupper portions of the ureters.

Sacral preganglionic axons leave the S2 to S4 segmentalnerves by gathering into the pelvic nerves. The pelvic nervesleave the sacral plexus on each side of the cord and distributetheir peripheral fibers to the bladder, uterus, urethra, prostate,distal portion of the transverse colon, descending colon, andrectum. The sacral parasympathetic fibers also supply the ve-nous outflow from the external genitalia to facilitate erectilefunction.

With the exception of cranial nerves III, VII, and IX, whichsynapse in discrete ganglia, the long parasympathetic pregan-glionic fibers pass uninterrupted to short postganglionic fiberslocated in the organ wall. In the walls of these organs, post-ganglionic neurons send axons to smooth muscle and glandu-lar cells that modulate their functions.


■ FIGURE 36-28 ■ Sympatheticpathways. Sympathetic fibersleave the spinal cord by way ofthe ventral root of the spinalnerves, enter the ventral primaryrami, and pass through the whiterami to the prevertebral or par-avertebral ganglia of the sympa-thetic chain, where they synapsewith postganglionic neurons.Some postganglionic fibers fromthe paravertebral ganglia reenterthe segmental nerves through thegray rami and are then distrib-uted in the spinal nerve branchesthat innervate the effector organs(eg., sweat glands and arrectorpili muscles of skin and vascularsmooth muscle of blood vessels).Other postganglionic neurons(dotted lines) travel directly totheir destination in the variouseffector organs.

To head (e.g., pupillary muscles)and carotid arteries with periarterial plexus

Spinal nerves toeffector organs in body

wall and limbs

To stomach andother abdominal

viscera

To lower limbs

Below L2

Above T1

Spinal cord

Intermedio-lateral horn

Ventral horn Spinalnerve

Ventralroot

Sympathetic trunk (chain)with paravertebral ganglia

Ventral anddorsal rami

Gray ramuscommunicans

White ramuscommunicans

Prevertebralganglion

Synapse

Splanchnicnerves

The gastrointestinal tract has its own intrinsic network ofganglionic cells located between the smooth muscle layers,called the enteric (or intramural) plexus, which controls localperistaltic movements and secretory functions. This network ofparasympathetic postganglionic neurons and interneuronsruns from the upper portion of the esophagus to the internalanal sphincter. Local afferent sensory neurons respond to me-chanical and chemical stimuli and communicate these influ-ences to motor fibers in the enteric plexus. The number of neu-rons in the enteric neural network (108) is so large that itapproximates that of the spinal cord. It is thought that this en-teric nervous system is capable of independent function with-out control from CNS fibers. The CNS has a modulating role,by way of preganglionic innervation of the plexus, convertinglocal peristalsis to longer-distance movements, thereby speed-ing the transit of intestinal contents.

Central Integrative PathwaysGeneral visceral afferent fibers accompany the sympathetic andparasympathetic outflow into the spinal and cranial nerves,bringing chemoreceptor, pressure, and nociceptive informa-tion from organs of the viscera to the brain stem, thoracolum-bar cord, and sacral cord. Local reflex circuits relating visceralafferent and autonomic efferent activity are integrated into ahierarchic control system in the spinal cord and brain stem.Progressively greater complexity in the responses and greaterprecision in their control occur at each higher level of the ner-vous system. Most visceral reflexes contain contributions fromthe LMNs that innervate skeletal muscles as part of their re-sponse patterns.

For most autonomic-mediated functions, the hypothala-mus serves as the major control center. The hypothalamus,which has connections with the cerebral cortex, the limbic sys-tem, and the pituitary gland, is in a prime position to receive,integrate, and transmit information to other areas of the ner-vous system. The neurons concerned with thermoregulation,thirst, and feeding behaviors are found in the hypothalamus.The hypothalamus also is the site for integrating neuroen-docrine function. Hypothalamic releasing and inhibiting hor-mones control the secretion of anterior pituitary hormones(see Chapter 30).

The organization of many life-support reflexes occurs in thereticular formation of the medulla and pons. These areas ofreflex circuitry, often called centers, produce complex combi-nations of autonomic and somatic efferent functions requiredfor the cough, sneeze, swallow, and vomit reflexes, as well asfor the more purely autonomic control of the cardiovascularsystem. At the hypothalamic level, these reflexes are integratedinto more general response patterns, such as rage, defensivebehavior, eating, drinking, voiding, and sexual function. Fore-brain and especially limbic system control of these behaviorsinvolves inhibiting or facilitating release of the response pat-terns according to social pressures during learned emotion-provoking situations.

Reflex adjustments of cardiovascular and respiratory func-tion occur at the level of the brain stem. A prominent exampleis the carotid sinus baroreflex (see Chapter 14). One of the strik-ing features of ANS function is the rapidity and intensity withwhich it can change visceral function. Within 3 to 5 seconds, itcan increase heart rate to approximately twice its resting level.

Bronchial smooth muscle tone is largely controlled by para-sympathetic fibers carried in the vagus nerve. These nerves pro-duce mild to moderate constriction of the bronchioles.

Other important ANS reflexes are located at the level of thespinal cord. As with other spinal reflexes, these reflexes aremodulated by input from higher centers. When there is loss ofcommunication between the higher centers and the spinal re-flexes, as occurs in spinal cord injury, these reflexes function inan unregulated manner (see Chapter 38).

Autonomic NeurotransmissionThe generation and transmission of impulses in the ANS occurin the same manner as in the CNS. There are self-propagatingaction potentials with transmission of impulses across syn-apses and other tissue junctions by way of neurohumoral trans-mitters. The postganglionic fibers of the ANS form a diffuseneural plexus at the site of innervation. The membranes of thecells of many smooth muscle fibers are connected by conduc-tive protoplasmic bridges, called gap junctions, that permit rapidconduction of impulses through whole sheets of smooth mus-cle, often in repeating waves of contraction. Autonomic neuro-transmitters released near a limited portion of these fibers pro-vide a modulating function extending to a large number ofeffector cells. The muscle layers of the gut and of the bladderwall are examples.

The main neurotransmitters of the autonomic nervous sys-tem are acetylcholine and the catecholamines, epinephrine andnorepinephrine. Acetylcholine is released at all of the sites ofpreganglionic transmission in the autonomic ganglia of sym-pathetic and parasympathetic nerve fibers and at the sites ofpostganglionic transmission in parasympathetic nerve endings.It also is released at sympathetic nerve endings that innervatethe sweat glands and cholinergic vasodilator fibers found inskeletal muscle. Norepinephrine is released at most sympa-thetic nerve endings. The adrenal medulla, which is a modifiedprevertebral sympathetic ganglion, produces epinephrine alongwith small amounts of norepinephrine. Dopamine, which is anintermediate compound in the synthesis of norepinephrine,also acts as a neurotransmitter. It is the principal inhibitorytransmitter of internuncial neurons in the sympathetic ganglia.It also has vasodilator effects on renal, splanchnic, and coro-nary blood vessels when given intravenously and is sometimesused in the treatment of shock (see Chapter 18).

Acetylcholine and Cholinergic ReceptorsAcetylcholine is synthesized in the cholinergic neurons fromcholine and acetyl coenzyme A (acetyl CoA). After acetylcho-line is secreted by the cholinergic nerve endings, it is rapidlybroken down by the enzyme acetylcholinesterase. The cholinemolecule is transported back into the nerve ending, where it isused again in the synthesis of acetylcholine.

Receptors that respond to acetylcholine are called choliner-gic receptors. There are two types of cholinergic receptors: mus-carinic and nicotinic. Muscarinic receptors are present on theinnervational targets of postganglionic fibers of the parasym-pathetic nervous system and the sweat glands, which are in-nervated by the sympathetic nervous system. Nicotinic recep-tors are found in autonomic ganglia and the end plates ofskeletal muscle. Acetylcholine has an excitatory effect on mus-carinic and nicotinic receptors, except for those in the heart and


lower esophagus, where it has an inhibitory effect. The drug at-ropine is an antimuscarinic or muscarinic cholinergic-blockingdrug that prevents the action of acetylcholine at excitatory andinhibitory muscarinic receptor sites. Because it is a muscarinic-blocking drug, it exerts little effect at nicotinic receptor sites.

Catecholamines and Adrenergic ReceptorsThe catecholamines, which include norepinephrine, epineph-rine, and dopamine, are synthesized in the sympathetic ner-vous system. Synthesis of dopamine and norepinephrine be-gins in the axoplasm of sympathetic nerve terminals with theconversion of the amino acid tyrosine to dopa; dopa to dopa-mine; and dopamine to norepinephrine. In the adrenal glandan additional step takes place during which approximately80% the norepinephrine is transformed into epinephrine.

Each of the steps in sympathetic neurotransmitter synthesisrequires a different enzyme, and the type of neurotransmitterthat is produced depends on the types of enzymes that areavailable in a nerve terminal. For example, the postganglionicsympathetic neurons that supply blood vessels have the neededenzymes for the synthesis of norepinephrine, whereas those inthe adrenal medulla have the enzymes needed to convert nor-epinephrine into epinephrine. As the catecholamines are syn-thesized, they are stored in vesicles. The final step of norepi-nephrine synthesis occurs in these vesicles. When an actionpotential reaches an axon terminal, the neurotransmitter mol-ecules are released from the storage vesicles. The storage vesi-cles provide a means for concentrated storage of the catechola-mines and protect them from the cytoplasmic enzymes thatdegrade the neurotransmitters.

In addition to neuronal synthesis, there is a second majormechanism for replenishment of norepinephrine in sympa-thetic nerve terminals. This mechanism consists of the active re-uptake of the released neurotransmitter into the nerve ter-minal. Between 50% and 80% of the norepinephrine that isreleased during an action potential is removed from the synap-tic area by an active reuptake process. This process terminatesthe action of the neurotransmitter and allows it to be reused by the neuron. The remainder of the released catecholaminesdiffuses into the surrounding tissue fluids or is degraded by twospecial enzymes: catechol-O-methyltransferase, which is dif-fusely present in all tissues, and monoamine oxidase (MAO),which is found in the nerve endings themselves.

Catecholamines can cause excitation or inhibition of smoothmuscle contraction, depending on the site, dose, and type ofreceptor present. The excitatory or inhibitory responses of or-gans to sympathetic neurotransmitters are mediated by inter-action with special structures in the cell membrane called re-ceptors. There are two types of sympathetic receptors: α andβ receptors. In vascular smooth muscle, excitation of α recep-tors causes vasoconstriction, and excitation of β-adrenergic re-ceptors causes vasodilatation. Constriction of blood vessels inthe skin, kidneys, and splanchnic circulation is mediated by α-adrenergic receptors. The β-adrenergic receptors are mostprevalent in the heart, the blood vessels of skeletal muscle, andthe bronchioles.

α-Adrenergic receptors have been further subdivided into α1

and α2 receptors, and β-adrenergic receptors into β1 and β2 re-ceptors. β1-Adrenergic receptors are found primarily in theheart and can be selectively blocked by β1-receptor–blockingdrugs. β2-Adrenergic receptors are found in the bronchioles and

in other sites that have β-mediated functions. The α1 receptorsare found primarily in postsynaptic effector sites; they mediateresponses in vascular smooth muscle. The α2 receptors aremainly located presynaptically and can inhibit the release ofnorepinephrine from sympathetic nerve terminals. The α2 re-ceptors are abundant in the CNS and are thought to influencethe central control of blood pressure.


In summary, the ANS regulates, adjusts, and coordinatesthe visceral functions of the body. The ANS, which is dividedinto the sympathetic and parasympathetic systems, is an ef-ferent system. It receives its afferent input from visceral affer-ent neurons. The ANS has CNS and PNS components. Theoutflow of the sympathetic and parasympathetic nervous sys-tem follows a two-neuron pathway, which consists of a pre-ganglionic neuron located in the CNS and a postganglionicneuron located outside the CNS. Sympathetic fibers leave theCNS at the thoracolumbar level, and the parasympatheticfibers leave at the craniosacral level.

In general, the sympathetic and parasympathetic nervoussystems have opposing effects on visceral function—if one ex-cites, the other inhibits. The hypothalamus serves as the majorcontrol center for most ANS functions; local reflex circuits re-lating visceral afferent and autonomic efferent activity are in-tegrated in a hierarchic control system in the spinal cord andbrain stem.

The main neurotransmitters for the ANS are acetylcholine,the catecholamines, epinephrine, and norepinephrine. Acetyl-choline is the transmitter for all preganglionic neurons, forpostganglionic parasympathetic neurons, and for selectedpostganglionic sympathetic neurons. The catecholamines arethe neurotransmitters for most postganglionic sympatheticneurons. The ANS neurotransmitters exert their action throughspecialized cell surface receptors—cholinergic receptors thatbind acetylcholine and adrenergic receptors that bind thecatecholamines. The cholinergic receptors are divided intonicotinic and muscarinic receptors, and adrenergic receptorsare divided into α and β receptors.

REVIEW QUESTIONS■ The nervous system functions in much the same way as acomputer system. Using this analogy, describe the relationshipbetween the PNS and CNS in terms of input, output, andcomputational functions.

■ The transmission of impulses in the nervous system occurs byway of chemical or electrical synapses. Compare the two typesof synapses in terms of mechanism of impulse generation,speed of conduction, one-way conduction, and in the case ofchemical synapses, the mechanism whereby the neurotransmit-ters are synthesized, stored, released, and inactivated.

■ The poliovirus produces paralysis of skeletal muscles but doesnot affect somatosensory or visceral function. Based on yourknowledge of cell columns, what neurons are susceptible toattack by the virus.

■ The inner tract layer of the nervous system contains many ofthe neuronal processes for reflexes such as those involved in

swallowing and vomiting. Explain the advantages of thisarrangement.

■ State the structures innervated by general somatic afferent,special visceral afferent, general visceral afferent, special so-matic afferent, general visceral efferent, pharyngeal efferent,and general somatic efferent neurons.

■ List the structures of the hindbrain, midbrain, and forebrainand describe their functions.

■ Name the cranial nerves and cite their location and function.

■ Describe the characteristics of the CSF and trace its passagethrough the ventricular system.

■ State the function of the autonomic nervous system.

■ Compare the anatomic location and functions of the sym-pathetic and parasympathetic nervous systems.

Visit the Connection site at connection.lww.com/go/porthfor links to chapter-related resources on the Internet.

BIBLIOGRAPHYAraque A., Parpura V., Sanzgiri R.P., et al. (1999). Tri-partite synapses:

Glia, the unacknowledged partner. Trends in Neuroscience 22, 208–215.Atkins D.L. (1998). Synapses. Step 4: Exploration of the neuron. [On-line].

Available: http://gwis2.circ.gwu.edu/~atkins/ Neuroweb/synapse.html.Accessed August 10, 2001.

Brodal P. (1998). The central nervous system: Structure and function (2nd ed.).New York: Oxford University Press.

Dambska M., Wisniewski K.E. (1999). Normal and pathologic developmentof the human brain and spinal cord. London: John Libbey & Company.

Gartner L.P., Hiatt J.L. (1997). Color textbook of histology (pp. 155–185).Philadelphia: W.B. Saunders.

Guyton A.C., Hall J.E. (2001). Textbook of medical physiology (10th ed.).Philadelphia: W.B. Saunders.

Haines D.E. (Ed.). (1997). Fundamental neuroscience (pp. 115–121, 126–127, 146–148, 443–454). New York: Churchill Livingstone.

Matthews G.G. (1998). Neurobiology: Molecules, cells, and systems. Malden,MA: Blackwell Science.

Moore K.L, Persaud T.V.N. (1998). The developing human: Clinically orientedembryology (6th ed., pp. 63–82, 451–490). Philadelphia: W.B. Saunders.

Parent A. (1996). Carpenter’s human neuroanatomy (9th ed., pp. 186–192,268–292, 748–756). Baltimore: Williams & Wilkins.

Zigmond M.J., Bloom E.F., Landis S.C., et al. (1999). Fundamental neuro-science. San Diego: Academic Press.


organization and control of the nervous systemfac.ksu.edu.sa › sites › default › files ›...

Documents