The Nervous System 161

They are specialized to respond to physical and chemical

Case Investigation stimuli, conduct electrochemical impulses, and release chem-
ical regulators. Through these activities, neurons enable the
Sandra’s grades have been improving, and she
perception of sensory stimuli, learning, memory, and the con-
treats herself to dinner at a seafood restaurant. However, after
trol of muscles and glands. Most neurons cannot divide by
just beginning to eat some mussels and clams gathered from
mitosis, although many can regenerate a severed portion or
the local seashore, she complains of severe muscle weak-
sprout small new branches under certain conditions.
ness. Paramedics are called, and when they examine Sandra,
Supporting cells aid the functions of neurons and are
they notice that she has a droopy eyelid and that her purse
about five times more abundant than neurons. In the CNS,
contains a prescription bottle for an MAO inhibitor. When
supporting cells are collectively called neuroglia, or simply
questioned, Sandra states that she had a recent Botox treat-
glial cells (from the Middle Greek glia = glue). Unlike neu-
ment, and the medication was prescribed to treat her clinical
rons, which do not divide mitotically (except for particular
depression. Further investigation reveals that the shellfish
neural stem cells; chapter 8, section 8.1), glial cells are able
were gathered from waters at the beginning of a red tide and
to divide by mitosis. This helps to explain why brain tumors
that Sandra’s blood pressure was in the normal range.
in adults are usually composed of glial cells rather than of
Some of the new terms and concepts you will
neurons.
encounter include:
■ Voltage-gated channels and the action of saxitoxin
■ Neurotransmitter release and the action of botulinum Neurons
toxin
■ Monoamine neurotransmitters and monoamine Although neurons vary considerably in size and shape,
oxidase (MAO) they generally have three principal regions: (1) a cell body,
(2) dendrites, and (3) an axon (figs. 7.1 and 7.2). Dendrites
and axons can be referred to generically as processes, or
extensions from the cell body.
The cell body is the enlarged portion of the neuron that
7.1 NEURONS AND contains the nucleus. It is the “nutritional center” of the neu-
ron where macromolecules are produced. The cell body and
SUPPORTING CELLS larger dendrites (but not axons) contain Nissl bodies, which
The nervous system is composed of neurons, which pro- are seen as dark-staining granules under the microscope.
Nissl bodies are composed of large stacks of rough endoplas-
duce and conduct electrochemical impulses, and sup-
mic reticulum that are needed for the synthesis of membrane
porting cells, which assist the functions of neurons. Neurons proteins. The cell bodies within the CNS are frequently clus-
are classified functionally and structurally; the various types tered into groups called nuclei (not to be confused with the
of supporting cells perform specialized functions. nucleus of a cell). Cell bodies in the PNS usually occur in
clusters called ganglia (table 7.1).

LEARNING OUTCOMES Dendrites Axon hillock

Direction of
conduction
After studying this section, you should be able to:
✔ Describe the different types of neurons and supporting Collateral axon
cells, and identify their functions.
✔ Identify the myelin sheath and describe how it is formed (a)
Cell body
in the CNS and PNS.
✔ Describe the nature and significance of the Axon
blood-brain barrier.

The nervous system is divided into the central nervous Axon

Direction of
system (CNS), which includes the brain and spinal cord, and conduction
the peripheral nervous system (PNS), which includes the
cranial nerves arising from the brain and the spinal nerves (b)
arising from the spinal cord.
Dendrites
The nervous system is composed of only two principal
types of cells—neurons and supporting cells. Neurons are the Figure 7.1 The structure of two kinds of neurons.
basic structural and functional units of the nervous system. A motor neuron (a) and a sensory neuron (b) are depicted here.

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 162 Chapter 7

Nucleus Dendrite

Node of Ranvier

Schwann
cell nucleus
Cell
body Myelinated
region Axon
Axon
hillock Unmyelinated
region
Myelin

Figure 7.2 Parts of a neuron. The axon of this neuron is wrapped by Schwann cells, which form a myelin sheath.

Table 7.1 | Terminology Pertaining to the Nervous System

Term Definition

Central nervous system (CNS) Brain and spinal cord

Peripheral nervous system (PNS) Nerves, ganglia, and nerve plexuses (outside of the CNS)

Association neuron (interneuron) Multipolar neuron located entirely within the CNS

Sensory neuron (afferent neuron) Neuron that transmits impulses from a sensory receptor into the CNS

Motor neuron (efferent neuron) Neuron that transmits impulses from the CNS to an effector organ; for example, a muscle

Nerve Cablelike collection of many axons in the PNS; may be “mixed” (contain both sensory and motor fibers)

Somatic motor nerve Nerve that stimulates contraction of skeletal muscles

Autonomic motor nerve Nerve that stimulates contraction (or inhibits contraction) of smooth muscle and cardiac muscle and that
stimulates glandular secretion

Ganglion Grouping of neuron cell bodies located outside the CNS

Nucleus Grouping of neuron cell bodies within the CNS

Tract Grouping of axons that interconnect regions of the CNS

Dendrites (from the Greek dendron = tree branch) are 400 mm/day) mainly transports membranous vesicles (impor-
thin, branched processes that extend from the cytoplasm of tant for synaptic transmission, as discussed in section 7.3).
the cell body. Dendrites provide a receptive area that trans- One slow component (at 0.2 to 1 mm/day) transports micro-
mits graded electrochemical impulses to the cell body. The filaments and microtubules of the cytoskeleton, while the
axon is a longer process that conducts impulses, called other slow component (at 2 to 8 mm/day) transports over
action potentials (section 7.2), away from the cell body. 200 different proteins, including those critical for synaptic
Axons vary in length from only a millimeter long to up function. The slow components appear to transport their
to a meter or more (for those that extend from the CNS cargo in fast bursts with frequent pauses, so that the overall
to the foot). The origin of the axon near the cell body is rate of transport is much slower than that occurring in the
an expanded region called the axon hillock; it is here that fast component.
action potentials originate. Side branches called axon col- Axonal transport may occur from the cell body to the
laterals may extend from the axon. axon and dendrites. This direction is called anterograde
Because axons can be quite long, special mechanisms transport, and involves molecular motors of kinesin proteins
are required to transport organelles and proteins from the that move cargo along the microtubules of the cytoskeleton
cell body to the axon terminals. This axonal transport is (chapter 3, section 3.2). For example, kinesin motors move
energy-dependent and is often divided into a fast component synaptic vesicles, mitochondria, and ion channels from the
and  two slow components. The fast component (at 200 to cell body through the axon. Similar anterograde transport

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 The Nervous System 163

Central Nervous System (CNS) Peripheral Nervous System (PNS)

Association neuron (interneuron)

Sensory neuron
Receptors

Somatic motor neuron

Skeletal
muscles

Autonomic motor neurons

Smooth muscle
Cardiac muscle
Glands

Autonomic ganglion

Figure 7.3 The relationship between CNS and PNS. Sensory and motor neurons of the peripheral nervous system carry
information into and out of, respectively, the central nervous system (brain and spinal cord).

occurs in the dendrites, as kinesin moves postsynaptic recep- effectors—smooth muscle, cardiac muscle, and glands. The
tors for neurotransmitters and ion channels along the micro- cell bodies of the autonomic neurons that innervate these
tubules in the dendrites. organs are located outside the CNS in autonomic ganglia
By contrast, axonal transport in the opposite direction— (fig. 7.3). There are two subdivisions of autonomic neu-
that is, along the axon and dendrites toward the cell body—is rons: sympathetic and parasympathetic. Autonomic motor
known as retrograde transport and involves molecular motor neurons, together with their central control centers, consti-
proteins of dyneins. The dyneins move membranes, vesicles, tute the autonomic nervous system, the focus of chapter 9.
and various molecules along microtubules of the cytoskeleton The structural classification of neurons is based on the
toward the cell body of the neuron. Retrograde transport can number of processes that extend from the cell body of the
also be responsible for movement of herpes virus, rabies virus, neuron (fig. 7.4). Pseudounipolar neurons have a single
and tetanus toxin from the nerve terminals into cell bodies. short process that branches like a T to form a pair of longer
processes. They are called pseudounipolar (from the Late
Latin pseudo = false) because, although they originate with
Classification of Neurons two processes, during early embryonic development their
two processes converge and partially fuse. Sensory neu-
and Nerves rons are pseudounipolar—one of the branched processes
Neurons may be classified according to their function or receives sensory stimuli and produces nerve impulses; the
structure. The functional classification is based on the other delivers these impulses to synapses within the brain
direction in which they conduct impulses, as indicated in or spinal cord. Anatomically, the part of the process that
figure 7.3. Sensory, or afferent, neurons conduct impulses conducts impulses toward the cell body can be considered a
from sensory receptors into the CNS. Motor, or efferent, dendrite, and the part that conducts impulses away from the
neurons conduct impulses out of the CNS to effector organs cell body can be considered an axon. Functionally, however,
(muscles and glands). Association neurons, or interneu- the branched process behaves as a single, long axon that
rons, are located entirely within the CNS and serve the asso- continuously conducts action potentials (nerve impulses).
ciative, or integrative, functions of the nervous system. Only the small projections at the receptive end of the pro-
There are two types of motor neurons: somatic and auto- cess function as typical dendrites, conducting graded electro-
nomic. Somatic motor neurons are responsible for both chemical impulses rather than action potentials. Bipolar
reflex and voluntary control of skeletal muscles. Autonomic neurons have two processes, one at either end; this type is
motor neurons innervate (send axons to) the involuntary found in the retina of the eye. Multipolar neurons, the most

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 164 Chapter 7

Pseudounipolar
Supporting Cells
Dendritic branches Unlike other organs that are “packaged” in connective tissue
derived from mesoderm (the middle layer of embryonic tis-
Bipolar sue), most of the supporting cells of the nervous system are
Dendrite
derived from the same embryonic tissue layer (ectoderm) that
produces neurons. The term neuroglia (or glia) traditionally
Multipolar Axon refers to the supporting cells of the CNS, but in current usage
Dendrites
the supporting cells of the PNS are often also called glial cells.

There are two types of supporting cells in the peripheral

nervous system:
1. Schwann cells (also called neurolemmocytes), which
form myelin sheaths around peripheral axons; and
2. satellite cells, or ganglionic gliocytes, which support
Figure 7.4 Three different types of neurons. neuron cell bodies within the ganglia of the PNS.
Pseudounipolar neurons, which are sensory, have one process that There are four types of supporting cells in the central
splits. Bipolar neurons, found in the retina and cochlea, have two nervous system (fig. 7.5):
processes. Multipolar neurons, which are motor and association
neurons, have many dendrites and one axon. 1. oligodendrocytes, which form myelin sheaths around
axons of the CNS;
2. microglia, which migrate through the CNS and
common type, have several dendrites and one axon extend- phagocytose foreign and degenerated material;
ing from the cell body; motor neurons are good examples 3. astrocytes, which help to regulate the external
of this type. environment of neurons in the CNS; and
A nerve is a bundle of axons located outside the CNS. Most 4. ependymal cells, which line the ventricles
nerves are composed of both motor and sensory fibers and are (cavities) of the brain and the central canal of
thus called mixed nerves. Some of the cranial nerves, however, the spinal cord.
contain sensory fibers only. These are the nerves that serve the
special senses of sight, hearing, taste, and smell. A bundle of Microglia are of hematopoietic (bone marrow) origin, and
axons in the CNS is called a tract. indeed can be replenished by monocytes (a type of leukocyte)

Capillary

Neurons

Astrocyte
Oligodendrocyte

Perivascular Axons
feet

Myelin sheath
Ependymal
cells

Cerebrospinal Microglia
fluid

Figure 7.5 The different types of neuroglial cells. Myelin sheaths around axons are formed in the CNS by oligodendrocytes.
Astrocytes have extensions that surround both blood capillaries and neurons. Microglia are phagocytic, and ependymal cells line the
brain ventricles and central canal of the spinal cord.

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 176 Chapter 7

Threshold

–60 mV Axon

–70 mV

+ + + + + + + + Action
potential begins
– – – – – – – –
Axon + – – + + + +
– – – – – – – – + + – – – –
+ + + + + + + + 1 Na+ Axon
+ + – – – –
– – + + + +

+ Action potential
is regenerated here
Injection of positive K+
charges (depolarization) + + – – + +
by stimulating electrode – – + + – –

Figure 7.18 Cable properties of an axon. The cable 2 Na+

properties of an axon are the properties that permit it to conduct – – + + – –
potential changes over distances. If a stimulating electrode + + – – + +
injects positive charges and produces a depolarization (blue) at K+
one point in the axon, the depolarization will quickly dissipate if it Action potential
+ is regenerated here
doesn’t trigger an action potential. The decreasing amplitude of K
the depolarization is due to leakage of charges through the axon + + + + – –
membrane (dashed arrows). This results in a poor ability of the – – – – + +
+
axon to conduct changes in potential over distances. 3 Na
– – – – + +
+ + + + – –
spread of charges and because many charges leak out of the axon K+
through its membrane (fig. 7.18). If an axon had to conduct only = resting potential
through its cable properties, therefore, no axon could be more = depolarization
than a millimeter in length. The fact that some axons are a meter
= repolarization
or more in length suggests that the conduction of nerve impulses
does not rely on the cable properties of the axon. Figure 7.19 The conduction of action potentials in
an unmyelinated axon. Each action potential “injects” positive
charges that spread to adjacent regions. The region that has just
produced an action potential is refractory. The next region, not
Conduction of Nerve Impulses having been stimulated previously, is partially depolarized. As a
When stimulating electrodes artificially depolarize one point result, its voltage-regulated Na+ gates open and the process is
of an axon membrane to a threshold level, voltage-regulated repeated. Successive segments of the axon thereby regenerate,
channels open and an action potential is produced at that or “conduct,” the action potential.
small region of axon membrane containing those channels.
For about the first millisecond of the action potential, when The action potential produced at the first location in the
the membrane voltage changes from −70 mV to +30 mV, axon membrane (usually at the axon hillock) thus serves as
a current of Na+ enters the cell by diffusion because of the the depolarization stimulus for the next region of the axon
opening of the Na+ gates. Each action potential thus “injects” membrane, which can then produce the action potential.
positive charges (sodium ions) into the axon (fig. 7.19). The action potential in this second region, in turn, serves
These positively charged sodium ions are conducted, by the as a depolarization stimulus for the production of the action
cable properties of the axon, to an adjacent region that still has potential in a third region, and so on. This explains how
a membrane potential of −70 mV. Within the limits of the cable the action potential is produced at all regions of the axon
properties of the axon (1 to 2 mm), this helps to depolarize the beyond the initial segment at the axon hillock. (The depo-
adjacent region of axon membrane. When this adjacent region larization stimulus for the action potential at the initial
of membrane reaches a threshold level of depolarization, it too segment of the axon results from synaptic transmission, dis-
produces the action potential as its voltage-regulated gates open. cussed in section 7.3.)

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 The Nervous System 177

Conduction in an Unmyelinated Axon the conduction. Because action potentials must be produced
at every fraction of a micrometer in an unmyelinated axon,
In an unmyelinated axon, every patch of membrane that con- the conduction rate is relatively slow. This conduction rate is
tains Na+ and K+ channels can produce an action potential. somewhat faster if the unmyelinated axon is thicker, because
Action potentials are thus produced along the entire length of thicker axons have less resistance to the flow of charges (so
the axon. The cablelike spread of depolarization induced by conduction of charges by cable properties is faster). The con-
the influx of Na+ during one action potential helps to depo- duction rate is substantially faster if the axon is myelinated,
larize the adjacent regions of membrane—a process that is because fewer action potentials are produced along a given
also aided by movements of ions on the outer surface of the length of myelinated axon.
axon membrane (fig. 7.19). This process would depolarize
the adjacent membranes on each side of the region to pro-
duce the action potential, but the area that had previously
produced one cannot produce another at this time because it Conduction in a Myelinated Axon
is still in its refractory period. The myelin sheath provides insulation for the axon, prevent-
It is important to recognize that action potentials are ing movements of Na+ and K+ through the membrane. If the
not really “conducted,” although it is convenient to use that myelin sheath were continuous, therefore, action potentials
word. Each action potential is a separate, complete event could not be produced. The myelin thus has interruptions—
that is repeated, or regenerated, along the axon’s length. This the nodes of Ranvier, as previously described.
is analogous to the “wave” performed by spectators in a sta- Because the cable properties of axons can conduct
dium. One person after another gets up (depolarization) and depolarizations over only a very short distance (1 to 2 mm),
then sits down (repolarization). It is thus the “wave” that the nodes of Ranvier cannot be separated by more than this
travels (the repeated action potential at different locations distance. Studies have shown that Na+ channels are highly
along the axon membrane), not the people. concentrated at the nodes (estimated at 10,000 per square
The action potential produced at the end of the axon is micrometer) and almost absent in the regions of axon
thus a completely new event that was produced in response membrane between the nodes. Action potentials, therefore,
to depolarization from the previous region of the axon mem- occur only at the nodes of Ranvier (fig. 7.20) and seem
brane. The action potential produced at the last region of to “leap” from node to node—a process called saltatory
the axon has the same amplitude as the action potential conduction (from the Latin saltario = leap). The leaping
produced at the first region. Action potentials are thus said is, of course, just a metaphor; the action potential at one
to  be conducted without decrement (without decreasing node depolarizes the membrane at the next node to thresh-
in amplitude). old, so that a new action potential is produced at the next
The spread of depolarization by the cable properties of node of Ranvier.
an axon is fast compared to the time it takes to produce an Myelinated axons conduct the action potential faster than
action potential. Thus, the more action potentials along a unmyelinated axons. This is because myelinated axons have
given stretch of axon that have to be produced, the slower voltage-gated channels only at the nodes of Ranvier, which

Action potential Action potential

was here now here
+
Na
a
Myelin

+ –– + +

– ++ – –
– ++ – –

+ –– + +
Axon

a+
Na

= Resting potential
= Depolarization
= Repolarization

Figure 7.20 The conduction of a nerve impulse in a myelinated axon. Because the myelin sheath prevents inward Na+
current, action potentials can be produced only at gaps in the myelin sheath called the nodes of Ranvier. This “leaping” of the action
potential from node to node is known as saltatory conduction.

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 178 Chapter 7

Table 7.3 | Conduction Velocities 7.3 THE SYNAPSE

and Functions of Mammalian Nerves
of Different Diameters Axons end close to, or in some cases at the point of con-
tact with, another cell. Once action potentials reach the
Diameter Conduction Examples of
(𝛍m) Velocity (m/sec) Functions Served
end of an axon, they directly or indirectly stimulate (or
inhibit) the other cell. In specialized cases, action poten-
12–22 70–120 Sensory: muscle position
tials can directly pass from one cell to another. In most
5–13 30–90 Somatic motor fibers cases, however, the action potentials stop at the axon
3–8 15–40 Sensory: touch, pressure terminal, where they stimulate the release of a chemical
1–5 12–30 Sensory: pain, temperature neurotransmitter that affects the next cell.
1–3 3–15 Autonomic fibers to ganglia

0.3–1.3 0.7–2.2 Autonomic fibers to smooth LEARNING OUTCOMES

and cardiac muscles
After studying this section, you should be able to:

are about 1 mm apart, whereas unmyelinated axons have ✔ Describe the structure and function of electrical and
chemical synapses.
these channels along their entire length. Because myelinated
axons have more cablelike spread of depolarization (which ✔ Identify the nature of excitatory and inhibitory
is faster), and fewer sites at which the action potential is postsynaptic potentials.
produced (which is slower) than unmyelinated axons, the
conduction is faster in a myelinated axon. Conduction rates A synapse is the functional connection between a neu-
in the human nervous system vary from 1.0 m/sec—in thin, ron and a second cell. In the CNS, this other cell is also a neu-
unmyelinated fibers that mediate slow, visceral responses— ron. In the PNS, the other cell may be either a neuron or an
to faster than 100 m/sec (225 miles per hour)—in thick, effector cell within a muscle or gland. Although the physiol-
myelinated fibers involved in quick stretch reflexes in skeletal ogy of neuron-neuron synapses and neuron-muscle synapses
muscles (table 7.3). is similar, the latter synapses are often called myoneural, or
In summary, the speed of action potential conduction neuromuscular, junctions.
is increased by (1) increased diameter of the axon, because Neuron-neuron synapses usually involve a connection
this reduces the resistance to the spread of charges by cable between the axon of one neuron and the dendrites, cell body,
properties; and (2) myelination, because the myelin sheath or axon of a second neuron. These are called, respectively,
results in saltatory conduction of action potentials. These axodendritic, axosomatic, and axoaxonic synapses. In almost
methods of affecting conduction speed are generally com- all synapses, transmission is in one direction only—from the
bined in the nervous system: the thinnest axons tend to be axon of the first (or presynaptic) neuron to the second (or
unmyelinated and the thickest tend to be myelinated. postsynaptic) neuron. Most commonly, the synapse occurs
between the axon of the presynaptic neuron and the den-
drites or cell body of the postsynaptic neuron.
| CHECKPOINT In the early part of the twentieth century, most physiolo-
6. Define the terms depolarization and repolarization, gists believed that synaptic transmission was electrical—that
and illustrate these processes graphically. is, that action potentials were conducted directly from one
7. Describe how the permeability of the axon cell to the next. This was a logical assumption, given that
membrane to Na+ and K+ is regulated and how nerve endings appeared to touch the postsynaptic cells and
changes in permeability to these ions affect the that the delay in synaptic conduction was extremely short
membrane potential. (about 0.5 msec). Improved histological techniques, how-
ever, revealed tiny gaps in the synapses, and experiments
8. Describe how gating of Na+ and K+ in the axon demonstrated that the actions of autonomic nerves could
membrane results in the production of an action potential. be duplicated by certain chemicals. This led to the hypoth-
9. Explain the all-or-none law of action potentials, and esis that synaptic transmission might be chemical—that the
describe the effect of increased stimulus strength on presynaptic nerve endings might release chemicals called
action potential production. How do the refractory periods neurotransmitters that stimulated action potentials in the
affect the frequency of action potential production? postsynaptic cells.
10. Describe how action potentials are conducted by In 1921 a physiologist named Otto Loewi published the
unmyelinated nerve fibers. Why is saltatory conduction results of experiments suggesting that synaptic transmis-
in myelinated fibers more rapid? sion was indeed chemical, at least at the junction between
a branch of the vagus nerve (chapter 9; see fig. 9.6) and the

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 The Nervous System 179

heart. He had isolated the heart of a frog and, while stimulat- Cytoplasm
ing the branch of the vagus that innervates the heart, per-
fused the heart with an isotonic salt solution. Stimulation Plasma
membrane
of the vagus nerve was known to slow the heart rate. After of one cell
stimulating the vagus nerve to this frog heart, Loewi col-
Plasma
lected the isotonic salt solution and then gave it to a second membrane
heart. The vagus nerve to this second heart was not stimu- of adjacent
cell
lated, but the isotonic solution from the first heart caused the
second heart to also slow its beat. Connexin
Two cells, proteins
Loewi concluded that the nerve endings of the vagus interconnected forming
by gap gap
must have released a chemical—which he called Vagusstoff— junctions Cytoplasm
junctions
that inhibited the heart rate. This chemical was subsequently
identified as acetylcholine, or ACh. In the decades follow- Figure 7.21 The structure of gap junctions. Gap
ing Loewi’s discovery, many other examples of chemical syn- junctions are water-filled channels through which ions can pass
apses were discovered, and the theory of electrical synaptic from one cell to another. This permits impulses to be conducted
transmission fell into disrepute. More recent evidence, ironi- directly from one cell to another. Each gap junction is composed
cally, has shown that electrical synapses do exist in the ner- of connexin proteins. Six connexin proteins in one plasma
vous system (though they are the exception), within smooth membrane line up with six connexin proteins in the other plasma
muscles, and between cardiac cells in the heart. membrane to form each gap junction.

Electrical Synapses: in the retina to increase in some neurons and decrease in

others.
Gap Junctions
In order for two cells to be electrically coupled, they must Chemical Synapses
be approximately equal in size and they must be joined by
areas of contact with low electrical resistance. In this way, Transmission across the majority of synapses in the ner-
impulses can be regenerated from one cell to the next with- vous system is one-way and occurs through the release of
out interruption. Adjacent cells that are electrically coupled chemical neurotransmitters from presynaptic axon endings.
are joined together by gap junctions. In gap junctions, the These presynaptic endings, called terminal boutons (from
membranes of the two cells are separated by only 2 nano- the Middle French bouton = button) because of their swol-
meters (1 nano meter = 10−9 meter). A surface view of len appearance, are separated from the postsynaptic cell by
gap junctions in the electron microscope reveals hexagonal a synaptic cleft so narrow (about 10 nm) that it can be seen
arrays of particles that function as channels through which clearly only with an electron microscope (fig. 7.22).
ions and molecules may pass from one cell to the next. Each
gap junction is now known to be composed of 12 proteins
known as connexins, which are arranged like staves of a bar-
rel to form a water-filled pore (fig. 7.21).
Gap junctions are present in cardiac muscle, where they
allow action potentials to spread from cell to cell, so that the
myocardium can contract as a unit. Similarly, gap junctions
in some smooth muscles allow many cells to be stimulated Mitochondria
Terminal
and contract together, producing a stronger contraction (as bouton of
in the uterus during labor). The function of gap junctions axon
in the nervous system is less well understood; neverthe-
less, gap junctions are found between neurons in the brain, Synaptic
where they can synchronize the firing of groups of neurons. vesicles
Gap junctions are also found between neuroglial cells, where
Synaptic
they are believed to allow the passage of Ca2+ and perhaps cleft
other ions and molecules between the connected cells. Postsynaptic
The function of gap junctions is more complex than was cell (skeletal
muscle)
once thought. Neurotransmitters and other stimuli, acting
through second messengers such as cAMP or Ca2+, can lead Figure 7.22 An electron micrograph of a chemical
to the phosphorylation or dephosphorylation of gap junc- synapse. This synapse between the axon of a somatic motor
tion connexin proteins, causing the opening or closing of neuron and a skeletal muscle cell shows the synaptic vesicles at
gap junction channels. For example, light causes the ion the end of the axon and the synaptic cleft. The synaptic vesicles
conductance through the gap junctions between neurons contain the neurotransmitter chemical.

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 180 Chapter 7

Chemical transmission requires that the synaptic cleft of synaptic vesicles undergoing exocytosis and releasing neu-
stay very narrow and that neurotransmitter molecules are rotransmitter molecules. As a result, a greater frequency of
released near their receptor proteins in the postsynaptic action potentials by the presynaptic axon will result in greater
membrane. The physical association of the pre- and post- stimulation of the postsynaptic neuron.
synaptic membranes at the chemical synapse is stabilized by Ca2+ entering the axon terminal binds to a protein,
the action of particular membrane proteins. Cell adhesion believed to be synaptotagmin, which serves as a Ca2+ sen-
molecules (CAMs) are proteins in the pre- and postsynaptic sor, forming a Ca2+-synaptotagmin complex in the cytoplasm.
membranes that project from these membranes into the syn- This occurs close to the location where synaptic vesicles are
aptic cleft, where they bond to each other. This Velcro-like already docked (attached) to the plasma membrane of the
effect ensures that the pre- and postsynaptic membranes stay axon terminal. At this stage, the docked vesicles are bound
in close proximity for rapid chemical transmission. to the plasma membrane of the presynaptic axon by com-
plexes of three SNARE proteins that bridge the vesicles and
Release of Neurotransmitter plasma membrane. The complete fusion of the vesicle mem-
brane and plasma membrane, and the formation of a pore
Neurotransmitter molecules within the presynaptic neuron
that allows the release of neurotransmitter, occurs when the
endings are contained within many small, membrane-enclosed
Ca2+-synaptotagmin complex displaces a component of the
synaptic vesicles (fig. 7.22). In order for the neurotransmit-
SNARE, or fusion, complex. This process is very rapid: exocy-
ter within these vesicles to be released into the synaptic cleft,
tosis of neurotransmitter occurs less than 100 microseconds
the vesicle membrane must fuse with the axon membrane
after the intracellular Ca2+ concentration rises.
in the process of exocytosis (chapter 3). Exocytosis of synap-
tic vesicles, and the consequent release of neurotransmitter
molecules into the synaptic cleft, is triggered by action poten-
tials that stimulate the entry of Ca2+ into the axon terminal Action of Neurotransmitter
through voltage-gated Ca2+ channels (fig. 7.23). When there is Once the neurotransmitter molecules have been released
a greater frequency of action potentials at the axon terminal, from the presynaptic axon terminals, they diffuse rapidly
there is a greater entry of Ca2+, and thus a larger number across the synaptic cleft and reach the membrane of the

Axon 1. Action potentials

Action terminal reach axon terminals
Ca2+ potentials Action
potentials

2. Voltage-gated Ca2+
Sensor protein channels open
+
Ca2+ Ca2+
Synaptic
Ca2+
vesicles

SNARE 3. Ca2+ binds to sensor

complex protein in cytoplasm
Docking

Ca2+ Ca2+
Fusion
Synaptic cleft

Exocytosis 4. Ca2+-protein complex

stimulates fusion and
exocytosis of
Neurotransmitter neurotransmitter
released
Postsynaptic cell
Ca2+

Figure 7.23 The release of neurotransmitter. Steps 1–4 summarize how action potentials stimulate the exocytosis of
synaptic vesicles. Action potentials open channels for Ca2+, which enters the cytoplasm and binds to a sensor protein, believed to be
synaptotagmin. Meanwhile, docked vesicles are held to the plasma membrane of the axon terminals by a complex of SNARE proteins.
The Ca2+-sensor protein complex alters the SNARE complex to allow the complete fusion of the synaptic vesicles with the plasma
membrane, so that neurotransmitters are released by exocytosis from the axon terminal.

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 The Nervous System 181

threshold required for action potentials. In other cases, as when

CLINICAL APPLICATION
CI− enters the cell through specific channels, a graded hyper-
Tetanus toxin and botulinum toxin are bacterial products that polarization is produced (where the inside of the postsynaptic
cause paralysis by preventing neurotransmission. These neuro- membrane becomes more negative). This hyperpolarization is
toxins function as proteases (protein-digesting enzymes), digest- called an inhibitory postsynaptic potential (IPSP) because the
ing particular components of the fusion complex and thereby membrane potential moves farther from the threshold depolar-
inhibiting the exocytosis of synaptic vesicles. Botulinum toxin ization required to produce action potentials. The mechanisms
destroys members of the SNARE complex of proteins needed for by which specific neurotransmitters produce graded EPSPs and
exocytosis of the neurotransmitter ACh, which stimulates muscle IPSPs will be described in the sections that follow.
contraction. This results in flaccid paralysis, where the muscles Excitatory postsynaptic potentials, as their name implies,
are unable to contract. Tetanus toxin acts similarly, but blocks stimulate the postsynaptic cell to produce action potentials,
inhibitory synapses in the CNS; this results in spastic paralysis, and inhibitory postsynaptic potentials antagonize this effect.
where the muscles are unable to relax. In synapses between the axon of one neuron and the den-
drites of another, the EPSPs and IPSPs are produced at the
dendrites and must propagate to the initial segment of the
axon to influence action potential production (fig. 7.24).

Case Investigation CLUES

Synaptic potentials
Botox is a preparation of botulinum toxin. (EPSPs and IPSPs)
Presynaptic
Sandra had ptosis (droopy eyelid), a side effect of her axon
Botox treatment.
Dendrites
■ By what action does Botox exert its effects?
■ How might this action be related to Sandra’s ptosis?
Integration

postsynaptic cell. The neurotransmitters then bind to specific Axon hillock

receptor proteins that are part of the postsynaptic mem-
brane. Receptor proteins have high specificity for their neu- Action potentials
initiated
rotransmitter, which is the ligand of the receptor protein.
The term ligand in this case refers to a smaller molecule (the
neurotransmitter) that binds to and forms a complex with a Node of Ranvier
larger protein molecule (the receptor). Binding of the neu-
rotransmitter ligand to its receptor protein causes ion chan-
nels to open in the postsynaptic membrane. The gates that Myelin sheath
regulate these channels, therefore, can be called chemically
regulated (or ligand-regulated) gates because they open in Impulse
Axon conduction
response to the binding of a chemical ligand to its receptor in
the postsynaptic plasma membrane.
Note that two broad categories of gated ion channels
have been described: voltage-regulated and chemically reg-
ulated. Voltage-regulated channels are found primarily in
the axons; chemically regulated channels are found in the
postsynaptic membrane. Voltage-regulated channels open in
response to depolarization; chemically regulated channels
open in response to the binding of postsynaptic receptor pro-
teins to their neurotransmitter ligands.
When the chemically regulated ion channels are opened,
they produce a graded change in the membrane potential,
also known as a graded potential. The opening of specific Neurotransmitter
release
channels—particularly those that allow Na+ or Ca2+ to enter
the cell—produces a graded depolarization, where the inside Figure 7.24 The functional specialization of
of the postsynaptic membrane becomes less negative. This different regions in a multipolar neuron. Integration of input
depolarization is called an excitatory postsynaptic potential (EPSPs and IPSPs) generally occurs in the dendrites and cell
(EPSP) because the membrane potential moves toward the body, with the axon serving to conduct action potentials.

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 182 Chapter 7

This is because the action potentials are first produced at

the initial segment of the axon, where there is a high density
| CHECKPOINT
of voltage-gated Na+ and K+ channels. The total depolariza- 11. Describe the structure, locations, and functions of gap
tion produced by the summation of EPSPs and IPSPs at the junctions.
initial segment of the axon will determine whether the axon 12. Describe the location of neurotransmitters within an axon
will fire action potentials, and the frequency with which it and explain the relationship between presynaptic axon
fires action potentials. Once the first action potentials are activity and the amount of neurotransmitters released.
produced, they will regenerate themselves along the axon as 13. Describe the sequence of events by which action
previously described. potentials stimulate the release of neurotransmitters
As shown in figure 7.24, the ligand (chemically) gated from presynaptic axons.
channels are located in the dendrites and cell body, so
14. Distinguish between voltage-regulated and chemically
that these regions can respond to neurotransmitter chemi-
regulated ion channels.
cals. The depolarization produced by those channels must
spread decrementally (with decreases in amplitude) to
the axon hillock, where the first action potentials are pro-
duced. After the depolarization stimulus (EPSP) causes
the opening of voltage-gated channels in the axon hill- 7.4 ACETYLCHOLINE AS
ock, the action potentials can be conducted without dec-
rement along the axon. These events are summarized in
A NEUROTRANSMITTER
figure 7.25. When acetylcholine (ACh) binds to its receptor, it directly
or indirectly causes the opening of chemically regulated
gates. In many cases, this produces a depolarization
called an excitatory postsynaptic potential, or EPSP. In
some cases, however, ACh causes a hyperpolarization
known as an inhibitory postsynaptic potential, or IPSP.
Presynaptic Action potentials
neuron conducted by axon
LEARNING OUTCOMES
Axon Opens voltage-gated
Ca2+ channels
After studying this section, you should be able to:
terminals
✔ Explain how ligand-gated channels produce synaptic
Release of excitatory
potentials, using the nicotinic ACh receptor as an example.
neurotransmitter ✔ Explain how G-protein-coupled channels produce
synaptic potentials, using the muscarinic ACh receptor
as an example.
✔ Describe the action and significance of
Postsynaptic Dendrites and Opens chemically (ligand) acetylcholinesterase.
neuron cell bodies gated channels

Inward diffusion of Na+ Acetylcholine (ACh) is used as an excitatory neurotrans-

causes depolarization (EPSP) mitter by some neurons in the CNS and by somatic motor
neurons at the neuromuscular junction. At autonomic nerve
Localized, decremental endings, ACh may be either excitatory or inhibitory, depend-
conduction of EPSP ing on the organ involved.
The varying responses of postsynaptic cells to the same
chemical can be explained, in part, by the fact that differ-
Axon hillock Opens voltage-gated Na+
and then K+ channels ent postsynaptic cells have different subtypes of ACh recep-
tors. These receptor subtypes can be specifically stimulated
by particular toxins, and they are named for these toxins.
Axon Conduction of action potential The stimulatory effect of ACh on skeletal muscle cells is pro-
duced by the binding of ACh to nicotinic ACh receptors, so
named because they can also be activated by nicotine. Effects
Figure 7.25 Events in excitatory synaptic of ACh on other cells occur when ACh binds to muscarinic
transmission. The different regions of the postsynaptic neuron ACh receptors; these effects can also be produced by mus-
are specialized, with ligand-(chemically) gated channels located carine (a drug derived from certain poisonous mushrooms).
in the dendrites and cell body, and voltage-gated channels An overview of the distribution of the two types of
located in the axon. ACh receptors demonstrates that this terminology and its

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 188 Chapter 7

Cell bodies
and dendrites
7.5 MONOAMINES AS
NEUROTRANSMITTERS
30
A variety of chemicals in the CNS function as neurotrans-
mitters. Among these are the monoamines, a chemical
family that includes dopamine, norepinephrine, and
serotonin. Although these molecules have similar mech-
anisms of action, they are used by different neurons for
different functions.

LEARNING OUTCOMES

After studying this section, you should be able to:

✔ Identify the monoamine neurotransmitters and explain
how they are inactivated at the synapse.
Figure 7.29 The graded nature of excitatory
postsynaptic potentials (EPSPs). Stimuli of increasing ✔ Identify two neural pathways in the brain that use
strength produce increasing amounts of depolarization. When a dopamine as a neurotransmitter, and explain their
threshold level of depolarization is produced, action potentials significance.
are generated in the axon.

Monoamines are regulatory molecules derived from

region, and so on. This chain of events ends at the terminal amino acids. Dopamine, norepinephrine (noradrenalin), and
boutons of the axon, where neurotransmitter is released. epinephrine (adrenalin) are derived from the amino acid
Alzheimer’s disease—the most common neurodegenera- tyrosine and placed in a subfamily of monoamines called
tive disease and the most common cause of senile dementia—is catecholamines. The term catechol refers to a common six-
associated with the loss of cholinergic neurons that terminate carbon ring structure, as shown in chapter 9, figure 9.8.
in the hippocampus and cerebral cortex, which are areas of the Dopamine is a neurotransmitter; norepinephrine is a neuro-
brain involved in memory storage (chapter 8). Possible causes transmitter and a hormone (from the adrenal medulla);
of Alzheimer’s disease are discussed in the Clinical Application and epinephrine is the primary hormone secreted by the
box on page 218; treatments currently include the use of cholin- adrenal medulla.
esterase (AChE) inhibitors to augment cholinergic transmission Other monoamines are derived from different amino
in the brain, and the use of antioxidants to limit the oxidative acids and so are not classified as catecholamines. Sero-
stress produced by free radicals (chapters 5 and 19), which con- tonin is derived from the amino acid tryptophan and
tribute to neural damage. functions as an important neurotransmitter. Histamine
is derived from the amino acid histidine and serves as a
| CHECKPOINT monoamine neurotransmitter, as well as a regulator pro-
duced by nonneural tissues. In the latter case, histamine
15. Distinguish between the two types of chemically stimulates gastric acid secretion, vasodilation, constric-
regulated channels and explain how ACh opens tion of the bronchioles (airways) in the lungs, and other
each type. functions in inflammation and allergy. As a monoamine
16. State a location at which ACh has stimulatory effects. neurotransmitter in the brain, histamine promotes wakeful
Where does it exert inhibitory effects? How are alertness; this is why some antihistamines cause drowsi-
stimulation and inhibition accomplished? ness (chapter 8, section 8.4).
Like ACh, monoamine neurotransmitters are released by
17. Describe the function of acetylcholinesterase and
exocytosis from presynaptic vesicles, diffuse across the syn-
discuss its physiological significance.
aptic cleft, and interact with specific receptor proteins in the
18. Compare the properties of EPSPs and action membrane of the postsynaptic cell. The stimulatory effects
potentials and state where these events occur in a of these monoamines, like those of ACh, must be quickly
postsynaptic neuron. inhibited so as to maintain proper neural control. The action
19. Explain how EPSPs produce action potentials in the of monoamine neurotransmitters at the synapse is stopped
postsynaptic neuron. by (1) reuptake of the neurotransmitter molecules from the
synaptic cleft into the presynaptic axon terminal, and then

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 The Nervous System 189

Presynaptic
neuron ending
1. Monoamine produced and
Action stored in synaptic vesicles
potentials
n Tyrosine
Ca2+ atio
Depolariz
Dopa
2. Action potentials open
gated Ca2+ channels,
leading to release of Dopamine 5. Inactivation of most
neurotransmitter neurotransmitter by MAO
Priming Norepinephrine

4. Reuptake of most
neurotransmitter
Fusion from synaptic cleft
3. Neurotransmitters
enter synaptic cleft

Norepinephrine
Receptor

Postsynaptic
cell

Figure 7.30 Production, release, reuptake, and inactivation of monoamine neurotransmitters. Most of the monoamine
neurotransmitters, including dopamine, norepinephrine, and serotonin, are transported back into the presynaptic axon terminals after
being released into the synaptic gap. They are then degraded and inactivated by an enzyme, monoamine oxidase (MAO).

(2) degradation of the monoamine by an enzyme within the

axon terminal called monoamine oxidase (MAO). This pro-
CLINICAL APPLICATION
cess is illustrated in figure 7.30. Monoamine oxidase (MAO) inhibitors are drugs that block
The monoamine neurotransmitters do not directly monoamine oxidase, the enzyme primarily responsible for
cause opening of ion channels in the postsynaptic mem- degrading the monoamine neurotransmitters. By preventing
brane. Instead, these neurotransmitters act by means of an the breakdown of monoamines, these drugs increase the
intermediate regulator, known as a second messenger. In amount of neurotransmitters in the synaptic cleft, promoting
the case of some synapses that use catecholamines for syn- their effects. MAO inhibitors have proven useful in the treat-
aptic transmission, this second messenger is a compound ment of clinical depression, suggesting that a deficiency in
known as cyclic adenosine monophosphate (cAMP). monoamine neurotransmission contributes to this disorder. An
Although other synapses can use other second messengers, MAO inhibitor drug is also used to treat Parkinson’s disease,
only the function of cAMP as a second messenger will be because it enhances the action of dopamine at the synapse. A
considered here. Other second-messenger systems are dis- serious potential side effect of MAO inhibitors is hypertensive
cussed in conjunction with hormone action in chapter 11, crisis (dangerously elevated blood pressure), because the
section 11.2. effects of epinephrine and norepinephrine (released by the
Binding of norepinephrine, for example, with its receptor sympathetic nerves and the adrenal medulla; chapter 9) act
in the postsynaptic membrane stimulates the dissociation of to raise the blood pressure. Hypertensive crisis may be pro-
the G-protein alpha subunit from the others in its complex voked in people taking MAO inhibitors by eating foods rich in
(fig. 7.31). This subunit diffuses in the membrane until it tyramine, a monoamine degraded by MAO that is found in
binds to an enzyme known as adenylate cyclase (also called cheese, preserved meats, and certain fish, among many other
adenylyl cyclase). This enzyme converts ATP to cyclic AMP foods. Tyramine can also cause migraine headaches in sus-
(cAMP) and pyrophosphate (two inorganic phosphates) ceptible people or those taking MAO inhibitors.
within the postsynaptic cell cytoplasm. Cyclic AMP in turn

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 to be modified by experience. Perceptions, learning, memory,
Case Investigation emotions, and perhaps even the self-awareness that forms
the basis of consciousness, are creations of the brain. Whim-
Frank, a 72-year-old man, is brought to the hos-
sical though it seems, the study of brain physiology is the
pital by his wife. She explains to the doctor that her hus-
process of the brain studying itself.
band suddenly became partially paralyzed and had
The study of the structure and function of the central
difficulty speaking. In the examination, the physician deter-
nervous system requires a knowledge of its basic “plan,”
mines that Frank is paralyzed on the right side of his body
which is established during the course of embryonic
but is able to produce a knee-jerk reflex with either leg.
development. The early embryo contains on its surface
When Frank is questioned, he speaks slowly and with
an embryonic tissue layer known as ectoderm; this will
great difficulty, but is coherent.
eventually form the epidermis of the skin, among other
Some of the new terms and concepts you will en-
structures. As development progresses, a groove appears
counter include:
in this ectoderm along the dorsal midline of the embryo’s
■ MRI, decussation of tracts, and cerebral lateralization body. This groove deepens, and by the twentieth day
■ Broca’s and Wernicke’s areas of the cerebral cortex, after conception it has fused to form a neural tube. The
and aphasias part of the ectoderm where the fusion occurs becomes a
■ Pyramidal motor system, descending tracts, and the separate structure called the neural crest, which is located
spinal reflex arc between the neural tube and the surface ectoderm (fig. 8.2).
Eventually the neural tube will become the central nervous
system, and the neural crest will become the ganglia of the
peripheral nervous system, among other structures.
By the middle of the fourth week after conception, three
distinct swellings are evident on the anterior end of the neu-
8.1 STRUCTURAL ORGANIZATION ral tube, which is going to form the brain: the forebrain
(prosencephalon), midbrain (mesencephalon), and hindbrain
OF THE BRAIN (rhombencephalon). During the fifth week, these areas
The brain is composed of an enormous number of asso- become modified to form five regions. The forebrain divides
ciation neurons and accompanying neuroglia, arranged into the telencephalon and diencephalon; the mesencephalon
remains unchanged; and the hindbrain divides into the met-
in regions and subdivisions. These neurons receive sen- encephalon and myelencephalon (fig. 8.3). These regions sub-
sory information, direct the activity of motor neurons, sequently become greatly modified, but the terms used here
and perform such higher brain functions as learning are also used to indicate general regions of the adult brain.
and memory.
Gyrus

Corpus callosum Sulcus

LEARNING OUTCOMES

After studying this section, you should be able to: Cerebrum

✔ Describe the embryonic origin of the CNS.

✔ Identify the five brain regions and the major structures
they contain.

The central nervous system (CNS), consisting of the

brain and spinal cord (fig. 8.1), receives input from sensory Tentorium
neurons and directs the activity of motor neurons that inner- Meninges cerebelli
vate muscles and glands. The association neurons within the
brain and spinal cord are in a position, as their name implies,
to associate appropriate motor responses with sensory stimuli, Cerebellum
Spinal cord
and thus to maintain homeostasis in the internal environment
Central canal
and the continued existence of the organism in a changing
external environment. Further, the central nervous systems of
all vertebrates (and most invertebrates) are capable of at least Figure 8.1 The CNS consists of the brain and the
rudimentary forms of learning and memory. This capability— spinal cord. Both of these structures are covered with
most highly developed in the human brain—permits behavior meninges and bathed in cerebrospinal fluid.

204

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 The Central Nervous System 207

Precentral Frontal poles

Superior frontal gyrus Central sulcus
gyrus Superior
Postcentral Longitudinal frontal gyrus
gyrus fissure
Superior Superior
frontal Parietal frontal
sulcus lobe sulcus

Frontal
lobe
Occipital Central
lobe sulcus

Lateral
sulcus
Temporal lobe Parietal
lobe
Cerebellar
hemisphere
Occipital poles
(a) (b)

Figure 8.5 The cerebrum. (a) A lateral view and (b) a superior view.

Motor areas involved with the Central sulcus

control of voluntary muscles
Sensory areas involved
with cutaneous and
other senses
Frontal lobe
Parietal lobe

Motor
speech area General
(Broca’s area) interpretive
area

Lateral
sulcus Occipital lobe

Combining visual
Auditory area images, visual
recognition of
Interpretation of sensory objects
experiences, memory of
visual and auditory patterns Figure 8.6 The lobes of the
Cerebellum left cerebral hemisphere. This
Temporal lobe diagram shows the principal motor and
Brain stem
sensory areas of the cerebral cortex.

The frontal lobe is the anterior portion of each cerebral The precentral (motor) and postcentral (sensory) gyri
hemisphere. A deep fissure, called the central sulcus, sep- have been mapped in conscious patients undergoing brain
arates the frontal lobe from the parietal lobe. The precen- surgery. Electrical stimulation of specific areas of the pre-
tral gyrus (figs. 8.5 and 8.6), involved in motor control, is central gyrus causes specific movements, and stimulation
located in the frontal lobe just in front of the central sulcus. of different areas of the postcentral gyrus evokes sensations
The cell bodies of the interneurons located here are called in specific parts of the body. Typical maps of these regions
upper motor neurons because of their role in muscle regu- (fig. 8.7) show an upside-down picture of the body, with the
lation (chapter 12). The postcentral gyrus, which is located superior regions of cortex devoted to the toes and the inferior
just behind the central sulcus in the parietal lobe, is the regions devoted to the head.
primary area of the cortex responsible for the perception of A striking feature of these maps is that the areas of cortex
somatesthetic sensation—sensation arising from cutaneous, responsible for different parts of the body do not correspond
muscle, tendon, and joint receptors. This neural pathway is to the size of the body parts being served. Instead, the body
described in chapter 10. regions with the highest densities of receptors are represented

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 208 Chapter 8

Central sulcus

Sensory area

Motor area

Upper Upper Pelvis Trunk Neck

Lower Trunk Upper
arm leg
Thumb, arm arm Lower
fingers, arm
Pelvis Lower
and hand Hand, fingers,
leg
and thumb
Facial Upper leg
expression Foot Upper
Lower leg and toes face
Foot Lips
Salivation and toes Genitals
Vocalization
Teeth
Mastication and gums
Longitudinal Tongue
Swallowing fissure and pharynx

Insula
Insula
Parietal lobes
Central sulcus

Motor area Frontal lobes Sensory area

(a) (b)

Figure 8.7 Motor and sensory areas of the cerebral cortex. (a) Motor areas that control skeletal muscles are shown in
yellow. This region is specifically known as the primary motor cortex (discussed later in this chapter). (b) Sensory areas that receive
somatesthetic sensations are shown in purple. Artistic license has been used in rendering part (b), because the left hemisphere receives
input primarily from the right side of the body.

Table 8.1 | Functions of the Cerebral Lobes by the largest areas of the sensory cortex, and the body regions
with the greatest number of motor innervations are repre-
Lobe Functions
sented by the largest areas of motor cortex. The hands and
Frontal Voluntary motor control of skeletal muscles; face, therefore, which have a high density of sensory receptors
personality; higher intellectual processes (e.g., and motor innervation, are served by larger areas of the pre-
concentration, planning, and decision making); central and postcentral gyri than is the rest of the body.
verbal communication
The temporal lobe contains auditory centers that receive
Parietal Somatesthetic interpretation (e.g., cutaneous and sensory fibers from the cochlea of each ear. This lobe is also
muscular sensations); understanding speech and involved in the interpretation and association of auditory and
formulating words to express thoughts and
emotions; interpretation of textures and shapes visual information. The occipital lobe is the primary area
responsible for vision and for the coordination of eye move-
Temporal Interpretation of auditory sensations; storage (memory) ments. The functions of the temporal and occipital lobes will
of auditory and visual experiences
be considered in more detail in chapter 10, in conjunction
Occipital Integration of movements in focusing the eye; with the physiology of hearing and vision.
correlation of visual images with previous visual The insula (fig. 8.7) is implicated in the encoding of
experiences and other sensory stimuli; conscious
perception of vision memory and in the integration of sensory information with
visceral responses. It receives olfactory, gustatory (taste),
Insula Memory; sensory (principally pain) and visceral auditory, and somatosensory (principally pain) information,
integration
and helps control autonomic responses to the viscera and

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 The Central Nervous System 209

cardiovascular system. Because it receives sensory informa- computed tomography (CT). CT involves complex computer
tion from the viscera, it is believed to be important in assess- manipulation of data obtained from x-ray absorption by tis-
ing the bodily states that accompany emotions. One study sues of different densities. Using this technique, soft tissues
demonstrated that those neurons that fire in response to pain such as the brain can be observed at different depths.
applied to the hand also fire when the subject was told that The next technique to be developed was positron
pain would be applied to the hand of a loved one; in another emission tomography (PET). In this technique, radioiso-
study, the neurons within the insula that responded to a dis- topes that emit positrons are injected into the bloodstream.
gusting odor also fired when the subject saw an expression Positrons are like electrons but carry a positive charge.
of disgust in another person. The collision of a positron and an electron results in their
Studies first performed in macaques demonstrated neu- mutual annihilation and the emission of gamma rays, which
rons in the frontal and parietal lobes that fired when the can be detected and used to pinpoint brain cells that are
monkeys performed goal-directed actions and when they most active. Medically, PET scans are used to determine the
observed others (monkeys and people) perform the same stage of cancer and to monitor patient responses to cancer
actions. These neurons, termed mirror neurons, have been treatments. Scientists have used PET to study brain metabo-
identified using fMRI (discussed next) in similar locations in lism, drug distribution in the brain, and changes in blood
the human brain. Mirror neurons help to integrate sensory flow as a result of brain activity.
and motor neural activity and also have neural connections, A newer technique for visualizing the living brain is mag-
through the insula, to the brain areas involved in emotions. netic resonance imaging (MRI). This technique is based on
Many scientists believe that mirror neurons are involved the concept that protons (H+), because they are charged and
in the ability to imitate others, understand the intentions spinning, are like little magnets. A powerful external magnet
and behavior of others, and empathize with the emotions can align a proportion of the protons. Most of the protons
displayed by others. These abilities are required for the are part of water molecules, and the chemical composition
acquisition of social skills and perhaps also of language, a of different tissues provides differences in the responses of
possibility supported by the observation that human mirror the aligned protons to a radio frequency pulse. This allows
neurons are found in Broca’s area, needed for language (see clear distinctions to be made between gray matter, white
fig. 8.14). Because autism, better termed autism spectrum matter, and cerebrospinal fluid (figs. 8.8 and 8.9). In addi-
disorder, involves impairments in social interactions, the tion, exogenous chemicals known as MRI contrast agents are
ability to imitate other people, language ability, and empa- sometimes used to increase or decrease the signal in different
thy (among other symptoms), some scientists have pro- tissues to improve the image.
posed that autism may be at least partly due to impairment Scientists can study the functioning brain in a living person
of mirror neuron function. using a technique known as functional magnetic resonance
imaging (fMRI). This technique visualizes increased neuronal
activity within a brain region indirectly, by the increased blood
Visualizing the Brain flow to the more active brain region (chapter 14; see fig. 14.22).
Several relatively new imaging techniques permit the brains This occurs because of increased release of the neurotransmit-
of living people to be observed in detail for medical and re- ter glutamate, which causes vasodilation and increased blood
search purposes. The first of these to be developed was x-ray flow in the more active brain regions. As a result, the active

Figure 8.8 An MRI image of the brain reveals the sensory cortex. The integration of MRI and EEG information shows the
location on the sensory cortex that corresponds to each of the digits of the hand.

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 216 Chapter 8

Limbic System and Emotion gyrus, which then completes the circuit by sending fibers to
the hippocampus. Through these interconnections, the lim-
The parts of the brain that appear to be of paramount impor- bic system and the hypothalamus appear to cooperate in the
tance in the neural basis of emotional states are the hypo- neural basis of emotional states.
thalamus (in the diencephalon) and the limbic system. Studies of the functions of these regions include elec-
The limbic system consists of a group of forebrain nuclei trical stimulation of specific locations, destruction of tissue
and fiber tracts that form a ring around the brain stem (producing lesions) in particular sites, and surgical removal,
(limbus = ring). Among the components of the limbic sys- or ablation, of specific structures. These studies suggest that
tem are the cingulate gyrus (part of the cerebral cortex), the the hypothalamus and limbic system are involved in the fol-
amygdaloid nucleus (or amygdala), the hippocampus, and lowing feelings and behaviors:
the septal nuclei (fig. 8.15). Studies also demonstrate that the
anterior insula is activated together with the anterior cingu- 1. Aggression. Stimulation of certain areas of the
late cortex during emotional experiences. amygdala produces rage and aggression, and
The limbic system was once called the rhinencephalon, stimulation of particular areas of the hypothalamus
or “smell brain,” because it is involved in the central pro- can produce similar effects.
cessing of olfactory information. This may be its primary 2. Fear. Fear can be produced by electrical stimulation of
function in lower vertebrates whose limbic system may the amygdala and hypothalamus, and surgical removal
constitute the entire forebrain. It is now known, however, of the limbic system can result in an absence of fear.
that the limbic system in humans is a center for basic Monkeys are normally terrified of snakes, for example,
emotional drives. The limbic system was derived early in but they will handle snakes without fear if their limbic
the course of vertebrate evolution, and its tissue is phylo- system is removed. Humans with damage to their
genetically older than the cerebral cortex. There are thus amygdala have demonstrated an impaired ability to
few synaptic connections between the cerebral cortex recognize facial expressions of fear and anger. These
and the structures of the limbic system, which perhaps and other studies suggest that the amygdala is needed
helps explain why we have so little conscious control for fear conditioning.
over our emotions. 3. Feeding. The hypothalamus contains both a feeding
There is a closed circuit of information flow between the center and a satiety center. Electrical stimulation of
limbic system and the thalamus and hypothalamus (fig. 8.15) the former causes overeating, and stimulation of the
called the Papez circuit. (The thalamus and hypothalamus latter will stop feeding behavior in experimental
are part of the diencephalon, described in a later section.) In animals.
the Papez circuit, a fiber tract, the fornix, connects the hip- 4. Sex. The hypothalamus and limbic system are involved
pocampus to the mammillary bodies of the hypothalamus, in the regulation of the sexual drive and sexual
which, in turn, project to the anterior nuclei of the thalamus. behavior, as shown by stimulation and ablation studies
The thalamic nuclei, in turn, send fibers to the cingulate in experimental animals. The cerebral cortex, however,

Corpus callosum
Fornix

Thalamus
Cingulate
gyrus Mammillary
body
Septal
Figure 8.15 The limbic system. The left nucleus Amygdala
temporal lobe has been removed in this figure to show
the structures of the limbic system (green). The limbic Preoptic nucleus
system consists of particular nuclei (aggregations of Olfactory bulb
neuron cell bodies) and axon tracts of the cerebrum Olfactory tract Hippocampus
that cooperate in the generation of emotions. The
Cortex of right
hypothalamus, though part of the diencephalon rather hemisphere
than the cerebrum (telencephalon), participates with the
limbic system in emotions. Hypothalamus

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 The Central Nervous System 217

is also critically important for the sex drive in lower People with amnesia have impaired declarative memory.
animals, and the role of the cerebrum is even more Scientists have discovered that the consolidation of short-
important for the sex drive in humans. term into long-term declarative memory is a function of the
5. Goal-directed behavior (reward and punishment medial temporal lobe, particularly of the hippocampus and
system). Electrodes placed in particular sites between amygdala (fig. 8.15). Although the hippocampus is important
the frontal cortex and the hypothalamus can deliver for maintaining recent memories, it is no longer needed once
shocks that function as a reward. In rats, this reward is the memory has become consolidated into a more stable,
more powerful than food or sex in motivating behavior. long-term form. An amnesiac patient known as “E.P.” with
Similar studies have been done in humans, who report bilateral damage to his medial temporal lobes, for example,
feelings of relaxation and relief from tension, but not of was able to remember well the neighborhood he left 50 years
ecstasy. Electrodes placed in slightly different positions before but had no knowledge of his current neighborhood.
apparently stimulate a punishment system in Using functional magnetic resonance imaging (fMRI) of
experimental animals, who stop their behavior when subjects asked to remember words, scientists detected more
stimulated in these regions. brain activity in the left medial temporal lobe and left frontal
lobe for words that were remembered compared to words
that were subsequently forgotten. The increased fMRI activ-
ity in these brain regions seems to indicate the encoding
Memory of the memories. Indeed, lesions of the left medial tempo-
ral lobe impairs verbal memory, while lesions of the right
Brain Regions in Memory medial temporal lobe impairs nonverbal memories, such as
Clinical studies of amnesia (loss of memory) suggest that the ability to remember faces.
several different brain regions are involved in memory stor- Surgical removal of the right and left medial temporal lobes
age and retrieval. Amnesia has been found to result from was performed in one patient, designated “H.M.,” in an effort
damage to the temporal lobe of the cerebral cortex, the hip- to treat his epilepsy. After the surgery he was unable to consoli-
pocampus, the head of the caudate nucleus (in Huntington’s date any short-term memory. He could repeat a phone number
disease), or the dorsomedial thalamus (in alcoholics suffer- and carry out a normal conversation; he could not remember
ing from Korsakoff’s syndrome with thiamine deficiency). the phone number if momentarily distracted, however, and if
A number of researchers now believe that there are several the person to whom he was talking left the room and came
different systems of information storage in the brain. One back a few minutes later, H.M. would have no recollection
system relates to the simple learning of stimulus-response of having seen that person or of having had a conversation
that even invertebrates can do to some degree. This, together with that person before. Although his memory of events that
with skill learning and different kinds of conditioning and occurred before the operation was intact, all subsequent events
habits, is retained in people with amnesia. in his life seemed as if they were happening for the first time.
There are different categories of memory, as revealed by H.M.’s deficit was in declarative memory. His nondeclara-
patients with particular types of brain damage and by numer- tive memory—perceptual and motor skills, such as how to drive
ous scientific investigations. Scientists distinguish between a car—were still intact. The effects of bilateral removal of H.M.’s
short-term memory and long-term memory. Long-term mem- medial temporal lobes were due to the fact that the hippocam-
ory, but not short-term memory, depends on the synthesis pus and amygdaloid nucleus (fig. 8.15) were also removed in
of new RNA and protein, so that drugs that disrupt genetic the process. Surgical removal of the left medial temporal lobe
transcription or translation interfere with long-term (but not impairs the consolidation of short-term verbal memories into
short-term) memory. People with head trauma, and patients long-term memory, and removal of the right medial temporal
who undergo electroconvulsive shock (ECS) therapy, may lose lobe impairs the consolidation of nonverbal memories.
their memory of recent events but retain their older memories. On the basis of additional clinical experience, it appears
The conversion of a short-term memory into a more stable that the hippocampus is a critical component of the memory
long-term memory is called memory consolidation. system. Magnetic resonance imaging (MRI) reveals that the
Long-term memory is classified as nondeclarative (or hippocampus is often shrunken in living amnesic patients.
implicit) memory and declarative (or explicit) memory. However, the degree of memory impairment is increased
Nondeclarative memory refers to memory of simple skills when other structures, as well as the hippocampus, are dam-
and conditioning (such as remembering how to tie shoe- aged. The hippocampus and associated structures of the
laces). Declarative memory is memory that can be verbal- medial temporal lobe are thus needed for the acquisition of
ized; it is subdivided into semantic (fact) and episodic new information about facts and events, and for the consoli-
(event) memory. A semantic memory would be remember- dation of short-term into long-term memory, which is stored
ing the names of the bones; an episodic memory would be in the cerebral cortex. Sleep, particularly slow-wave (non-
remembering the experience of taking a practical exam on REM) sleep, but perhaps also REM sleep, is needed for opti-
the skeletal system. mum memory consolidation by the hippocampus. Emotional

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 218 Chapter 8

arousal, acting via the structures of the limbic system, can as backtracking to pick up an item you skipped while browsing
enhance or inhibit long-term memory storage. For example, in a new store. However, both types of working memory require
stress has been shown to produce deficits in hippocampus- the prefrontal cortex. There are also certain generalities that
dependent learning and memory. can be made about long-term declarative memory and brain
The amygdala appears to be particularly important in location. For example, the ability to recall names and categories
the memory of fear responses. Studies demonstrate increased (semantic memory) is localized to the inferior temporal lobes;
neural activity of the human amygdala during visual pro- different locations seem to be required for storing episodic
cessing of fearful faces, and patients with bilateral damage memories. Thus, in Alzheimer’s disease, episodic and semantic
to the amygdala were unable to read danger when shown memory decline independently of each other.
threatening pictures. Much remains to be learned about the brain locations asso-
The cerebral cortex is thought to store factual informa- ciated with different systems of memory (table 8.3). Continued
tion, with verbal memories lateralized to the left hemisphere scientific investigations, including fMRI studies, patient obser-
and visuospatial information to the right hemisphere. The vations, and others, will yield important new information about
neurosurgeon Wilder Penfield was the first to electrically the relationship between different anatomical brain regions and
stimulate various brain regions of awake patients, often evok- their roles in memory storage, consolidation, and retrieval.
ing visual or auditory memories that were extremely vivid.
Electrical stimulation of specific points in the temporal lobe
evoked specific memories so detailed that the patients felt as CLINICAL APPLICATION
if they were reliving the experience. The medial regions of
the temporal lobes, however, cannot be the site where long- People with Alzheimer’s disease have (1) a loss of neurons in
term memory is stored because destruction of these areas in the hippocampus and cerebral cortex; (2) an accumulation of
patients being treated for epilepsy did not destroy the mem- intracellular proteins forming neurofibrillar tangles; and (3) an
ory of events prior to the surgery. The inferior temporal accumulation of extracellular protein deposits called senile
lobes, on the other hand, do appear to be sites for the stor- plaques. The major constituent of these plaques is a protein
age of long-term visual memories. called amyloid b-peptide (Aβ). Aβ is formed by cleavage of a
The left inferior frontal lobe has recently been shown larger precursor protein (abbreviated APP ) by enzymes called
to participate in performing exact mathematical calcula- a, b, and g -secretase. The enzyme γ-secretase catalyzes the
tions. Scientists have speculated that this brain region may be formation of the particular Aβ peptide that has the greatest
involved because it stores verbally coded facts about num- medical significance. This peptide, 42 amino acids long, forms
bers. Using fMRI, researchers have recently demonstrated clumps of the most toxic insoluble fibers that cause death of
that complex problem-solving involves the most anterior neighboring neurons. People with inherited forms of early-
portion of the frontal lobes, an area called the prefrontal onset Alzheimer’s disease have mutations that increase the
cortex. Some of the other functions ascribed to the prefrontal amount of this peptide product of γ-secretase.
cortex include short-term memory (as for a phone number The majority of Alzheimer’s disease cases are classified as
that must be kept in mind to dial but then quickly forgotten), “sporadic”—they don’t run in families, and they probably result
planning (remembering to perform sequential actions), and from the interaction between many genes and the environ-
the inhibition of inappropriate actions (such as answering a ment. The causes of the sporadic form are not well under-
stranger’s ringing telephone). There is evidence that signals stood. The progression of the disease is correlated with the Aβ
are sent from the prefrontal cortex to the inferior temporal “burden,” but the destruction of neurons may be promoted by
lobes, where visual long-term memories are stored. Lesions other factors, such as the polypeptide fragment produced
of the prefrontal cortex interfere with memory in a less dra- when APP is cleaved to form Aβ. For reasons not yet fully
matic way than lesions of the medial temporal lobe. understood, people with a particular allele (form) of the gene
The amount of memory destroyed by ablation (removal) for apolipoprotein E (a cholesterol carrier protein active in the
of brain tissue seems to depend more on the amount of brain brain) are 3 to 4 times more likely to develop Alzheimer’s dis-
tissue removed than on the location of the surgery. On the ease between the ages of 60 to 70 years.
basis of these observations, it was formerly believed that the Clinical observations support the notion that an intellectu-
memory was diffusely located in the brain; stimulation of ally rich and physically active lifestyle may offer some protection
the correct location of the cortex then retrieved the memory. against Alzheimer’s disease, perhaps by building up a “cogni-
According to current thinking, however, particular aspects of tive reserve.” There is also evidence that eating a diet restricted
the memory—visual, auditory, olfactory, spatial, and so on— in calories and saturated fats, and enriched in vitamins C, E, and
are stored in particular areas, and the cooperation of all of folate, may afford some protection. Once Alzheimer’s disease is
these areas is required to elicit the complete memory. present, the symptoms are mostly treated with drugs that inhibit
As an example of the diffuse location of memories, work- acetylcholinesterase (AChE) activity. This is because Alzheimer’s
ing memory—the ability to keep information in your head disease causes the destruction of cholinergic neurons, and
consciously for a short time—is stored differently depending on drugs that inhibit the inactivation of ACh promote transmission
whether it involves keeping several numbers in your mind until by the surviving cholinergic neurons.
you type them, or whether it involves spatial information, such

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 232 Chapter 8

fibers. Those cranial nerves associated with the special senses

| CHECKPOINT (e.g., olfactory, optic), however, consist of sensory fibers only.
14. Explain why each cerebral hemisphere receives The cell bodies of these sensory neurons are not located in the
sensory input from and directs motor output to the brain, but instead are found in ganglia near the sensory organ.
contralateral side of the body.
15. List the tracts of the pyramidal motor system and
describe the function of the pyramidal system.
16. List the tracts of the extrapyramidal system and explain
Spinal Nerves
how this system differs from the pyramidal motor system. There are 31 pairs of spinal nerves. These nerves are grouped
into 8 cervical, 12 thoracic, 5 lumbar, 5 sacral, and 1 coc-
cygeal according to the region of the vertebral column from
which they arise (fig. 8.27).
Each spinal nerve is a mixed nerve composed of sen-
8.6 CRANIAL AND SPINAL NERVES sory and motor fibers. These fibers are packaged together
The central nervous system communicates with the in the nerve, but they separate near the attachment of
the nerve to the spinal cord. This produces two “roots”
body by means of nerves that exit the CNS from the to each nerve. The dorsal root is composed of sensory
brain (cranial nerves) and spinal cord (spinal nerves). fibers, and the ventral root is composed of motor fibers
These nerves, together with aggregations of cell bodies (fig. 8.28). An enlargement of the dorsal root, the dorsal
located outside the CNS, constitute the peripheral ner- root ganglion, contains the cell bodies of the sensory neu-
rons. The motor neuron shown in figure 8.28 is a somatic
vous system. motor neuron that innervates skeletal muscles; its cell
body is not located in a ganglion but instead is contained
within the gray matter of the spinal cord. The cell bodies of
LEARNING OUTCOMES some autonomic motor neurons (which innervate involun-
tary effectors), however, are located in ganglia outside the
After studying this section, you should be able to: spinal cord (the autonomic system is discussed separately
✔ Identify the structures of a spinal nerve and describe in chapter 9).
the neural pathways of a reflex arc

As mentioned in chapter 7, the peripheral nervous sys- Reflex Arc

tem (PNS) consists of nerves (collections of axons) and their The functions of the sensory and motor components of a
associated ganglia (collections of cell bodies). Although this spinal nerve can be understood most easily by examining
chapter is devoted to the CNS, the CNS cannot function with- a simple reflex; that is, an unconscious motor response to
out the PNS. This section thus serves to complete our discus- a sensory stimulus. Figure 8.28 demonstrates the neural
sion of the CNS and introduces concepts pertaining to the pathway involved in a reflex arc. Stimulation of sensory
PNS that will be explored more thoroughly in later chapters receptors evokes action potentials that are conducted into
(particularly chapters 9, 10, and 12). the spinal cord by sensory neurons. In the example shown,
a sensory neuron synapses with an association neuron (or
interneuron), which, in turn, synapses with a somatic motor
neuron. The somatic motor neuron then conducts impulses
Cranial Nerves out of the spinal cord to the muscle and stimulates a reflex
Of the 12 pairs of cranial nerves, 2 pairs arise from neuron contraction. Notice that the brain is not directly involved in
cell bodies located in the forebrain and 10 pairs arise from the this reflex response to sensory stimulation. Some reflex arcs
midbrain and hindbrain. The cranial nerves are designated are even simpler than this; in a muscle stretch reflex (the
by Roman numerals and by names. The Roman numerals knee-jerk reflex, for example) the sensory neuron synapses
refer to the order in which the nerves are positioned from the directly with a motor neuron. Other reflexes are more com-
front of the brain to the back. The names indicate the struc- plex, involving a number of association neurons and result-
tures innervated by these nerves (e.g., facial) or the principal ing in motor responses on both sides of the spinal cord at
function of the nerves (e.g., oculomotor). A summary of the different levels. These skeletal muscle reflexes are described
cranial nerves is presented in table 8.6. together with muscle control in chapter 12, and autonomic
Most cranial nerves are classified as mixed nerves. This reflexes, involving smooth and cardiac muscle, are described
term indicates that the nerve contains both sensory and motor in chapter 9.

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 The Central Nervous System 235

Upper motor neuron

(association neuron
in brain)
Dorsal root Dorsal
ganglion root
Cell body of
neuron
Sensory neuron

Somatic
motor neuron

Association neuron

Spinal
nerve

Spinal cord Ventral

root

Skeletal muscle

Figure 8.28 Activation of somatic motor neurons. Somatic motor neurons may be stimulated by spinal association neurons,
as shown here, or directly by sensory neurons, in a reflex arc that doesn’t involve the brain. The spinal association neurons and motor
neurons can also be stimulated by association neurons (called upper motor neurons) in the motor areas of the brain. This affords
voluntary control of skeletal muscles.

SUMMARY
8.1 Structural Organization of the Brain 204 8.2 Cerebrum 206
A. During embryonic development, five regions of the brain A. The cerebrum consists of two hemispheres connected by
are formed: the telencephalon, diencephalon, mesenceph- a large fiber tract called the corpus callosum.
alon, metencephalon, and myelencephalon.
1. The outer part of the cerebrum, the cerebral cortex,
1. The telencephalon and diencephalon constitute the consists of gray matter.
forebrain; the mesencephalon is the midbrain, and the
2. Under the gray matter is white matter, but nuclei of
hindbrain is composed of the metencephalon and the
gray matter, known as the basal nuclei, lie deep within
myelencephalon.
the white matter of the cerebrum.
2. The CNS begins as a hollow tube, and thus the brain
3. Synaptic potentials within the cerebral cortex
and spinal cord are hollow. The cavities of the brain
produce the electrical activity seen in an
are known as ventricles.
electroencephalogram (EEG).

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 Autonomic motor nerves innervate organs whose func-
Case Investigation tions are not usually under voluntary control. The effectors
that respond to autonomic regulation include cardiac mus-
Cathy has asthma, and had to use her inhaler
cle (the heart), smooth muscles, and glands. These effec-
before taking her physiology exam. Later, in the physiology
tors are part of the visceral organs (organs within the body
laboratory, she measured her pulse rate and blood pres-
cavities) and of blood vessels. The involuntary effects of
sure and found them to be higher than usual. The following
autonomic innervation contrast with the voluntary control of
week, after administering some drugs (epinephrine, atro-
skeletal muscles by way of somatic motor neurons.
pine, and others) to a frog heart, she later developed a
severe headache and dry mouth. When she looked in the
mirror she noticed that her pupils were dilated.
Some of the new terms and concepts you will
encounter include: Autonomic Neurons
■ Adrenergic effects and fight-or-flight Neurons of the peripheral nervous system (PNS) that
■ Alpha- and beta-adrenergic receptors and their conduct impulses away from the central nervous system
agonists and antagonists (CNS) are known as motor, or efferent, neurons (chapter 7,
■ Muscarinic cholinergic effects and atropine section 7.1). There are two major categories of motor
neurons: somatic and autonomic. Somatic motor neurons
have their cell bodies within the CNS and send axons to
skeletal muscles, which are usually under voluntary con-
trol. This was briefly described in chapter 8 (see fig. 8.28),
in the section on the reflex arc. The control of skeletal
9.1 NEURAL CONTROL OF muscles by somatic motor neurons is discussed in depth
INVOLUNTARY EFFECTORS in chapter 12, section 12.5.
The autonomic nervous system helps regulate the activi- Unlike somatic motor neurons, which conduct impulses
along a single axon from the spinal cord to the neuromuscular
ties of cardiac muscle, smooth muscles, and glands. In
junction, autonomic motor control involves two neurons
this regulation, impulses are conducted from the CNS by in the efferent pathway (fig. 9.1 and table 9.1). The first
an axon that synapses with a second autonomic neuron. of these neurons has its cell body in the gray matter of
It is the axon of this second neuron in the pathway that the brain or spinal cord. The axon of this neuron does not
directly innervate the effector organ but instead synapses
innervates the involuntary effectors.
with a second neuron within an autonomic ganglion (a gan-
glion is a collection of cell bodies outside the CNS). The
first neuron is thus called a preganglionic neuron. The
LEARNING OUTCOMES second neuron in this pathway, called a postganglionic
neuron, has an axon that extends from the autonomic gan-
After studying this section, you should be able to:
glion to an effector organ, where it synapses with its target
✔ Describe the organization of autonomic motor neurons tissue (fig. 9.1).
✔ Describe how neural regulation of smooth and cardiac Preganglionic autonomic fibers originate in the midbrain
muscles differs from neural regulation of skeletal muscles and hindbrain and in the upper thoracic to the fourth sacral
levels of the spinal cord. Autonomic ganglia are located in the

Autonomic
CNS ganglion
Involuntary
Figure 9.1 The autonomic system effector
has preganglionic and postganglionic
neurons. The preganglionic neurons of the
autonomic system have cell bodies in the CNS,
whereas the postganglionic neurons have cell Smooth
bodies within autonomic ganglia. The muscle
sympathetic and parasympathetic divisions
differ in the particular locations of their Preganglionic Postganglionic
preganglionic neuron cell bodies within the neuron neuron
CNS, and in the location of their ganglia.

240

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 The Autonomic Ner vous System 241

Table 9.1 | Comparison of the Somatic Motor System and the Autonomic Motor System
Feature Somatic Motor Autonomic Motor

Effector organs Skeletal muscles Cardiac muscle, smooth muscle, and glands

Presence of ganglia No ganglia Cell bodies of postganglionic autonomic fibers

located in paravertebral, prevertebral (collateral),
and terminal ganglia

Number of neurons from CNS to effector One Two

Type of neuromuscular junction Specialized motor end plate No specialization of postsynaptic membrane; all
areas of smooth muscle cells contain receptor
proteins for neurotransmitters

Effect of nerve impulse on muscle Excitatory only Either excitatory or inhibitory

Type of nerve fibers Fast-conducting, thick (9–13μm), and Slow-conducting; preganglionic fibers lightly
myelinated myelinated but thin (3μm); postganglionic fibers
unmyelinated and very thin (about 1.0μm)

Effect of denervation Flaccid paralysis and atrophy Muscle tone and function persist; target cells show
denervation hypersensitivity

head, neck, and abdomen; chains of autonomic ganglia also Unlike skeletal muscles, which enter a state of flaccid
parallel the right and left sides of the spinal cord. The origin paralysis and atrophy when their motor nerves are sev-
of the preganglionic fibers and the location of the autonomic ered, the involuntary effectors are somewhat independent
ganglia help to distinguish the sympathetic and parasympa- of their innervation. Smooth muscles maintain a resting
thetic divisions of the autonomic system, discussed in later tone (tension) in the absence of nerve stimulation, for
sections of this chapter. example. In fact, damage to an autonomic nerve makes
The sensory neurons that conduct information from its target tissue more sensitive than normal to stimulating
the viscera for autonomic nerve reflexes can have the same agents. This phenomenon is called denervation hyper-
anatomy as those sensory neurons involved in somatic sensitivity. Such compensatory changes can explain
motor reflexes (chapter 8, fig. 8.28). That is, the sensory why, for example, the ability of the stomach mucosa to
information enters the spinal cord on the dorsal roots of secrete acid may be restored after its neural supply from
the spinal nerves. However, some important visceral sen- the vagus nerve has been severed. (This procedure is called
sory information can instead enter the brain in cranial vagotomy, and is sometimes performed as a treatment
nerves. For example, information about blood pressure, for ulcers.)
plasma pH, and oxygen concentration is carried into the In addition to their intrinsic (“built-in”) muscle tone,
brain by sensory axons in cranial nerves IX and X. These cardiac muscle and many smooth muscles take their auton-
are mixed nerves, containing both sensory and parasympa- omy a step further. These muscles can contract rhythmi-
thetic motor axons. cally, even in the absence of nerve stimulation, in response
to electrical waves of depolarization initiated by the mus-
cles themselves. Autonomic innervation simply increases
or decreases this intrinsic activity. Autonomic nerves also
Visceral Effector Organs maintain a resting tone, in the sense that they maintain a
Because the autonomic nervous system helps regulate the baseline firing rate that can be either increased or decreased.
activities of glands, smooth muscles, and cardiac muscle, A decrease in the excitatory input to the heart, for example,
autonomic control is an integral aspect of the physiology of will slow its rate of beat.
most of the body systems. Autonomic regulation, then, plays The release of acetylcholine (ACh) from somatic motor
roles in endocrine regulation (chapter 11), smooth muscle neurons always stimulates the effector organ (skeletal mus-
function (chapter 12), the functions of the heart and circu- cles). By contrast, some autonomic nerves release transmit-
lation (chapters 13 and 14), and, in fact, all the remaining ters that inhibit the activity of their effectors. An increase
systems to be discussed. Although the functions of the target in the activity of the vagus, a nerve that supplies inhibitory
organs of autonomic innervation are described in subsequent fibers to the heart, for example, will slow the heart rate,
chapters, at this point we will consider some of the common whereas a decrease in this inhibitory input will increase the
features of autonomic regulation. heart rate.

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 242 Chapter 9

The sympathetic and parasympathetic divisions of the

| CHECKPOINT autonomic system have some structural features in common.
1. Describe the preganglionic and postganglionic Both consist of preganglionic neurons that originate in the
neurons in the autonomic system. Use a diagram to CNS and postganglionic neurons that originate outside of the
illustrate the difference in efferent outflow between CNS in ganglia. However, the specific origin of the pregan-
somatic and autonomic nerves. glionic fibers and the location of the ganglia differ in the two
divisions of the autonomic system.
2. Compare the control of cardiac muscle and smooth
muscles with that of skeletal muscles. How is each type
of muscle tissue affected by cutting its innervation? Sympathetic Division
The sympathetic division is also called the thoracolumbar divi-
sion of the autonomic system because its preganglionic fibers
9.2 DIVISIONS OF THE AUTONOMIC exit the spinal cord, in the ventral roots of spinal nerves, from the
first thoracic (T1) to the second lumbar (L2) levels. Most sym-
NERVOUS SYSTEM pathetic nerve fibers, however, separate from the somatic motor
Preganglionic neurons of the sympathetic division origi- fibers and synapse with postganglionic neurons within a dou-
nate in the thoracic and lumbar levels of the spinal cord ble row of sympathetic ganglia, called paravertebral ganglia,
located on either side of the spinal cord (fig. 9.2). Ganglia within
and send axons to sympathetic ganglia, which parallel each row are interconnected, forming a sympathetic chain of
the spinal cord. Preganglionic neurons of the parasym- ganglia that parallels the spinal cord on each lateral side.
pathetic division originate in the brain and in the sacral The myelinated preganglionic sympathetic axons exit the
level of the spinal cord, and send axons to ganglia spinal cord in the ventral roots of spinal nerves, but they
soon diverge from the spinal nerves within short pathways
located in or near the effector organs. called white rami communicantes. The axons within each
ramus enter the sympathetic chain of ganglia, where they
can travel to ganglia at different levels and synapse with
LEARNING OUTCOMES postganglionic sympathetic neurons. The axons of the post-
ganglionic sympathetic neurons are unmyelinated and form
After studying this section, you should be able to:
the gray rami communicantes as they return to the spinal
✔ Describe the structure of the sympathetic and nerves and travel as part of the spinal nerves to their effec-
parasympathetic divisions of the autonomic system tor organs (fig. 9.3). Because sympathetic axons form a com-
✔ Explain the relationships between the sympathetic ponent of spinal nerves, they are widely distributed to the
division and the adrenal medulla skeletal muscles and skin of the body, where they innervate
blood vessels and other involuntary effectors.

Spinal cord
Posterior (dorsal) root Sympathetic chain of
Anterior (ventral) root paravertebral ganglia

Rami communicantes Sympathetic ganglion

Spinal nerve Vertebral body

Rib

Figure 9.2 The sympathetic chain of paravertebral ganglia. This diagram shows the anatomical relationship between the
sympathetic ganglia and the vertebral column and spinal cord.

fox78119_ch09_239-262.indd 242 02/07/10 7:02 PM

 The Autonomic Ner vous System 243

1. Preganglionic axons Visceral effectors: 2. Postganglionic

synapse with Smooth muscle of axons innervate
postganglionic blood vessels, arrector target organs
neurons pili muscles, and
sweat glands
Sympathetic
Dorsal root chain
ganglion ganglion
Dorsal Spinal
root nerve Sympathetic chain

White ramus
Splanchnic
Ventral root nerve

Gray ramus Visceral effector:

intestine

Collateral
ganglion
(celiac ganglion)

Preganglionic neuron
Spinal cord Postganglionic neuron

Figure 9.3 The pathway of sympathetic neurons. The preganglionic neurons enter the sympathetic chain of ganglia on the white
ramus (one of the two rami communicantes). Some synapse there, and the postganglionic axon leaves on the gray ramus to rejoin a spinal
nerve. Others pass through the ganglia without synapsing. These ultimately synapse in a collateral ganglion, such as the celiac ganglion.

Divergence occurs within the sympathetic chain of gan- different glands with different embryonic origins, different
glia as preganglionic fibers branch to synapse with numerous hormones, and different regulatory mechanisms. The adre-
postganglionic neurons located in ganglia at different levels nal cortex secretes steroid hormones; the adrenal medulla
in the chain. Convergence also occurs here when a postgan- secretes the hormone epinephrine (adrenaline) and, to a
glionic neuron receives synaptic input from a large number lesser degree, norepinephrine, when it is stimulated by the
of preganglionic fibers. The divergence of impulses from the sympathetic system.
spinal cord to the ganglia and the convergence of impulses The adrenal medulla can be likened to a modified
within the ganglia results in the mass activation of almost all sympathetic ganglion; its cells are derived from the same
of the postganglionic sympathetic neurons. This explains why embryonic tissue (the neural crest, chapter 8) that forms
the sympathetic system is usually activated as a unit, affecting postganglionic sympathetic neurons. Like a sympathetic
all of its effector organs at the same time. However, it does ganglion, the cells of the adrenal medulla are innervated
appear that the sympathetic division can increase its stimula- by preganglionic sympathetic fibers. The adrenal medulla
tion of a particular organ, such as the heart, in some cases. secretes epinephrine into the blood in response to this
neural stimulation. The effects of epinephrine are comple-
Collateral Ganglia mentary to those of the neurotransmitter norepinephrine,
which is released from postganglionic sympathetic nerve
Many preganglionic fibers that exit the spinal cord below the
endings. For this reason, and because the adrenal medulla
level of the diaphragm pass through the sympathetic chain
is stimulated as part of the mass activation of the sympa-
of ganglia without synapsing. Beyond the sympathetic chain,
thetic system, the two are often grouped together as a single
these preganglionic fibers form splanchnic nerves. Pregangli-
sympathoadrenal system.
onic fibers in the splanchnic nerves synapse in collateral, or
prevertebral, ganglia. These include the celiac, superior mes-
enteric, and inferior mesenteric ganglia (fig. 9.4). Postgan-
glionic fibers that arise from the collateral ganglia innervate Parasympathetic Division
organs of the digestive, urinary, and reproductive systems.
The parasympathetic division is also known as the cranio-
sacral division of the autonomic system. This is because its
Adrenal Glands preganglionic fibers originate in the brain (specifically, in the
The paired adrenal glands are located above each kidney. midbrain, pons, and medulla oblongata) and in the second
Each adrenal is composed of two parts: an outer cortex and through fourth sacral levels of the spinal column. These pre-
an inner medulla. These two parts are really two functionally ganglionic parasympathetic fibers synapse in ganglia that

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 244 Chapter 9

Diaphragm

Celiac ganglion
Superior mesenteric
ganglion

Renal plexus
First lumbar
sympathetic Aortic
ganglion plexus

Inferior mesenteric
ganglion

Pelvic sympathetic
chain

Figure 9.4 The collateral sympathetic ganglia. These include the celiac ganglion and the superior and inferior mesenteric ganglia.

Table 9.2 | The Sympathetic Division

Parts of Body Innervated Spinal Origin of Preganglionic Fibers Origin of Postganglionic Fibers

Eye C8 and T1 Cervical ganglia

Head and neck T1 to T4 Cervical ganglia

Heart and lungs T1 to T5 Upper thoracic (paravertebral) ganglia

Upper extremities T2 to T9 Lower cervical and upper thoracic (paravertebral) ganglia

Upper abdominal viscera T4 to T9 Celiac and superior mesenteric (collateral) ganglia

Adrenal T10 and T11 Not applicable

Urinary and reproductive systems T12 to L2 Celiac and interior mesenteric (collateral) ganglia

Lower extremities T9 to L2 Lumbar and upper sacral (paravertebral) ganglia

are located next to—or actually within—the organs inner- Four of the 12 pairs of cranial nerves (chapter 8, section 8.6)
vated. These parasympathetic ganglia, called terminal gan- contain preganglionic parasympathetic fibers. These are the
glia, supply the postganglionic fibers that synapse with the oculomotor (III), facial (VII), glossopharyngeal (IX), and vagus
effector cells. (X) nerves. Parasympathetic fibers within the first three of these
The comparative structures of the sympathetic and para- cranial nerves synapse in ganglia located in the head; fibers in
sympathetic divisions are listed in tables 9.2 and 9.3, and the vagus nerve synapse in terminal ganglia located in wide-
illustrated in figure 9.5. It should be noted that most para- spread regions of the body. Cranial nerves IX and X contain
sympathetic fibers do not travel within spinal nerves, as do sensory axons as well as parasympathetic motor axons: they
sympathetic fibers. As a result, cutaneous effectors (blood are mixed nerves. Visceral sensory information (from blood
vessels, sweat glands, and arrector pili muscles) and blood pressure receptors in certain arteries, for example) evokes
vessels in skeletal muscles receive sympathetic but not para- autonomic reflex motor responses (of heart rate, for example).
sympathetic innervation. These reflexes will be discussed in chapter 14.

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 The Autonomic Ner vous System 245

Table 9.3 | The Parasympathetic Division

Origin of Location of
Nerve Preganglionic Fibers Terminal Ganglia Effector Organs
Oculomotor (third cranial) nerve Midbrain (cranial) Ciliary ganglion Eye (smooth muscle in iris and ciliary body)

Facial (seventh cranial) Pons (cranial) Pterygopalatine and Lacrimal, mucous, and salivary glands
submandibular ganglia

Glossopharyngeal (ninth cranial) Medulla oblongata (cranial) Otic ganglion Parotid gland
nerve

Vagus (tenth cranial) nerve Medulla oblongata (cranial) Terminal ganglia in or near organ Heart, lungs, gastrointestinal tract, liver,
pancreas

Pelvic spinal nerves S2 to S4 (sacral) Terminal ganglia near organs Lower half of large intestine, rectum,
urinary bladder, and reproductive organs

Cranial nerve III

Ciliary muscle and
pupil of eye
Midbrain Cranial nerve VII
Lacrimal gland
Hindbrain Cranial nerve IX and nasal mucosa

Cranial nerve X
Submandibular
and sublingual
T1 glands
T2
T3 Parotid gland

T4
T5 Lung
T6

T7 Celiac
Sympathetic chain
ganglion
ganglion
T8 Heart
Greater splanchnic
T9 nerve
Liver and gallbladder
T10
Spleen
T11
Lesser splanchnic Stomach
T12 nerve
Pancreas
L1
Superior
L2 mesenteric
ganglion Large intestine
Small intestine

Adrenal gland
and kidney
S2
S3 Inferior
mesenteric
S4
ganglion

Urinary bladder
Pelvic nerves

Reproductive
organs

Figure 9.5 The autonomic nervous system. The sympathetic division is shown in red; the parasympathetic in blue. The solid
lines indicate preganglionic fibers, and the dashed lines indicate postganglionic fibers.

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 246 Chapter 9

The oculomotor nerve contains somatic motor and para- these preganglionic fibers branch from the main trunks of
sympathetic fibers that originate in the oculomotor nuclei of the vagus nerves and synapse with postganglionic neurons
the midbrain. These parasympathetic fibers synapse in the located within the innervated organs. The preganglionic
ciliary ganglion, whose postganglionic fibers innervate the vagus fibers are thus quite long; they provide parasympa-
ciliary muscle and constrictor fibers in the iris of the eye. thetic innervation to the heart, lungs, esophagus, stomach,
Preganglionic fibers that originate in the pons travel in the pancreas, liver, small intestine, and the upper half of the
facial nerve to the pterygopalatine ganglion, which sends large intestine. Postganglionic parasympathetic fibers arise
postganglionic fibers to the nasal mucosa, pharynx, palate, from terminal ganglia within these organs and synapse with
and lacrimal glands. Another group of fibers in the facial effector cells (smooth muscles and glands).
nerve terminates in the submandibular ganglion, which Preganglionic fibers from the sacral levels of the spi-
sends postganglionic fibers to the submandibular and sub- nal cord provide parasympathetic innervation to the lower
lingual salivary glands. Preganglionic fibers of the glosso- half of the large intestine, the rectum, and to the urinary
pharyngeal nerve synapse in the otic ganglion, which sends and  reproductive systems. These fibers, like those of the
postganglionic fibers to innervate the parotid salivary gland. vagus, synapse with terminal ganglia located within the
Nuclei in the medulla oblongata contribute pregangli- effector organs.
onic fibers to the very long tenth cranial, or vagus, nerves Parasympathetic nerves to the visceral organs thus con-
(the “vagrant” or “wandering” nerves), which provide the sist of preganglionic fibers, whereas sympathetic nerves to
major parasympathetic innervation in the body. These pre- these organs contain postganglionic fibers. An overall view
ganglionic fibers travel through the neck to the thoracic cav- of the autonomic nervous system, with a comparison of the
ity and through the esophageal opening in the diaphragm sympathetic and parasympathetic divisions, can be obtained
to the abdominal cavity (fig. 9.6). In each region, some of by reviewing figure 9.5.

Hyoid bone
Vagus nerve
Thyroid cartilage of larynx

Trachea

Right pulmonary plexus

Right cardiac branch Left pulmonary plexus

Left cardiac branch

Right gastric nerve Left gastric nerve

Celiac plexus
Stomach

Liver

Superior
mesenteric nerve

Figure 9.6 The path of the vagus nerves. The vagus nerves and their branches provide parasympathetic innervation to most
organs within the thoracic and abdominal cavities.

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 The Autonomic Ner vous System 247

The effects of parasympathetic nerve stimulation are

| CHECKPOINT in many ways opposite to those produced by sympathetic
3. Describe the sympathetic pathway from the CNS to the stimulation. The parasympathetic system, however, is not
(a) heart; and (b) adrenal gland. normally activated as a whole. Stimulation of separate para-
sympathetic nerves can result in slowing of the heart, dila-
4. Explain the functional relationship between the
tion of visceral blood vessels, and increased activity of the
sympathetic division and the adrenal glands.
digestive tract (table 9.4). Visceral organs respond differently
5. Describe the parasympathetic pathway to the eye and to sympathetic and parasympathetic nerve activity because
to the heart, identifying the neurons involved. the postganglionic fibers of these two divisions release differ-
ent neurotransmitters.

9.3 FUNCTIONS OF THE

AUTONOMIC NERVOUS SYSTEM
CLINICAL APPLICATION
The sympathetic division of the autonomic system acti-
Cocaine blocks the reuptake of dopamine and norepinephrine
vates the body to “fight or flight,” largely through the
into the presynaptic axon terminals. This causes an excessive
release of norepinephrine from postganglionic fibers and amount of these neurotransmitters to remain in the synaptic
the secretion of epinephrine from the adrenal medulla. cleft and stimulate their target cells. Because sympathetic nerve
The parasympathetic division often produces antagonis- effects are produced mainly by the action of norepinephrine,
cocaine is a sympathomimetic drug (a drug that promotes
tic effects through the release of acetylcholine from its
sympathetic nerve effects). This can result in vasoconstric-
postganglionic fibers. tion of coronary arteries, leading to heart damage (myocardial
ischemia, myocardial infarction, and left ventricular hypertro-
phy). The combination of cocaine with alcohol is more deadly
LEARNING OUTCOMES
than either drug taken separately, and is a common cause of
After studying this section, you should be able to: death from substance abuse.

✔ Identify the neurotransmitters of the sympathetic and

parasympathetic divisions, and the hormone released
by the adrenal medulla
✔ Describe the effects of adrenergic stimulation on
different organs, and identify the types of adrenergic Adrenergic and Cholinergic
receptors involved Synaptic Transmission
✔ Describe the effects of parasympathetic nerve Acetylcholine (ACh) is the neurotransmitter of all pre-
regulation, and explain how atropine and related drugs
ganglionic fibers (both sympathetic and parasympathetic).
affect this regulation
Acetylcholine is also the transmitter released by most para-
sympathetic postganglionic fibers at their synapses with
The sympathetic and parasympathetic divisions of the effector cells (fig. 9.7). Transmission at these synapses is
autonomic system affect the visceral organs in different ways. thus said to be cholinergic.
Mass activation of the sympathetic system prepares the body The neurotransmitter released by most postganglionic
for intense physical activity in emergencies; the heart rate sympathetic nerve fibers is norepinephrine (noradrenaline).
increases, blood glucose rises, and blood is diverted to the Transmission at these synapses is thus said to be adrenergic.
skeletal muscles (away from the visceral organs and skin). There are a few exceptions, however. Some sympathetic
These and other effects are listed in table 9.4. The theme fibers that innervate blood vessels in skeletal muscles, as
of the sympathetic system has been aptly summarized in a well as sympathetic fibers to sweat glands, release ACh
phrase: “fight or flight.” There is no such universally recog- (are cholinergic).
nized phrase to describe the actions of the parasympathetic Since the cells of the adrenal medulla are embryologi-
system. However, because many of its actions are opposite cally related to postganglionic sympathetic neurons, it is not
to those of the sympathetic division, the theme of the para- surprising that their hormones are epinephrine (about 85%)
sympathetic division might be described as rest and digest, and norepinephrine (about 15%). Epinephrine differs from
or repast and repose. An examination of table 9.4 will reveal norepinephrine only in that the former has an additional
how many organs respond to sympathetic and parasympa- methyl (CH3) group, as shown in figure 9.8. Epinephrine, nor-
thetic nerve regulation. epinephrine, and dopamine (a transmitter within the  CNS)

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 248 Chapter 9

Table 9.4 | Effects of Autonomic Nerve Stimulation on Various Effector Organs

Effector Organ Sympathetic Effect Parasympathetic Effect

Eye

Iris (radial muscle) Dilation of pupil —

Iris (sphincter muscle) — Constriction of pupil

Ciliary muscle Relaxation (for far vision) Contraction (for near vision)

Glands

Lacrimal (tear) — Stimulation of secretion

Sweat Stimulation of secretion —

Salivary Saliva becomes thick Increased secretion; saliva becomes thin

Stomach — Stimulation of secretion

Intestine — Stimulation of secretion

Adrenal medulla Stimulation of hormone secretion —

Heart

Rate Increased Decreased

Conduction Increased rate Decreased rate

Strength Increased —

Blood Vessels Mostly constriction; affects all organs Dilation in a few organs (e.g., penis)

Lungs

Bronchioles (tubes) Dilation Constriction

Mucous glands Inhibition of secretion Stimulation of secretion

Gastrointestinal Tract

Motility Inhibition of movement Stimulation of movement

Sphincters Closing stimulated Closing inhibited

Liver Stimulation of glycogen hydrolysis —

Adipose (Fat) Cells Stimulation of fat hydrolysis —

Pancreas Inhibition of exocrine secretions Stimulation of exocrine secretions

Spleen Contraction —

Urinary Bladder Muscle tone aided Contraction

Arrector Pili Muscles Erection of hair and goose bumps —

Uterus If pregnant: contraction; if not pregnant: relaxation —

Penis Ejaculation Erection (due to vasodilation)

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 The Autonomic Ner vous System 249

Cranial Terminal
parasympathetic ganglion
nerves Visceral
ACh
ACh effectors

Paravertebral
ganglion
NE Visceral
ACh effectors

Adrenal
medulla
Sympathetic ACh E, NE (hormones)
(thoracolumbar) Circulation
nerves

NE Visceral
ACh effectors
Sacral Collateral
parasympathetic ganglion
nerves
Figure 9.7 Neurotransmitters of
the autonomic motor system.
ACh = acetylcholine; NE = norepinephrine;
E = epinephrine. Those nerves that release
Visceral
effector ACh are called cholinergic; those nerves that
ACh ACh
organs release NE are called adrenergic. The
adrenal medulla secretes both epinephrine
(85%) and norepinephrine (15%) as
hormones into the blood.

are all derived from the amino acid tyrosine and are collec- muscles of the iris, and the smooth muscles of many blood
tively termed catecholamines (fig. 9.8). vessels are stimulated to contract. The smooth muscles of
Where the axons of postganglionic autonomic neurons the bronchioles and of some blood vessels, however, are
enter into their target organs, they have numerous swell- inhibited from contracting; adrenergic chemicals, therefore,
ings, called varicosities, that contain the neurotransmit- cause these structures to dilate.
ter molecules. Neurotransmitters can thereby be released Because excitatory and inhibitory effects can be pro-
along a length of axon, rather than just at the axon ter- duced in different tissues by the same neurotransmitter, the
minal. Thus, autonomic neurons are said to form synapses responses must depend on the characteristics of the cells. To
en passant (“synapses in passing”) with their target cells some degree, this is due to the presence of different membrane
(fig. 9.9). Sympathetic and parasympathetic axons often receptor proteins for the catecholamine neurotransmitters.
innervate the same target cells, where they release differ- (The interaction of neurotransmitters and receptor proteins in
ent neurotransmitters that promote different (and usually the postsynaptic membrane was described in chapter 7.) The
antagonistic) effects. two major classes of these receptor proteins are designated
alpha- (α) and beta- (β) adrenergic receptors.
Experiments have revealed that each class of adrenergic
Responses to Adrenergic receptor has two major subtypes. These are designated by
subscripts: α1 and α2; β1 and β2. Compounds have been devel-
Stimulation oped that selectively bind to one or the other type of adren-
Adrenergic stimulation—by epinephrine in the blood and by ergic receptor and, by this means, either promote or inhibit
norepinephrine released from sympathetic nerve endings— the normal action produced when epinephrine or norepineph-
has both excitatory and inhibitory effects. The heart, dilatory rine binds to the receptor. As a result of its binding to an

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 250 Chapter 9

H H
Tyrosine Varicosity
HO C C NH2 Sympathetic
(an amino acid)
neuron
H COOH Smooth muscle cell
Synapses
en passant

HO Parasympathetic
H H neuron
DOPA
HO C C NH2
(dihydroxyphenylalanine)
H COOH

(a)

HO
H H
Dopamine
HO C C NH2
(a neurotransmitter)
H H Axon of Sympathetic
Neuron
Synaptic vesicle
with norepinephrine (NE)
HO
H H
Norepinephrine NE
(a neurotransmitter HO C C NH2
and hormone)
OH H

Adrenergic
receptors
OH
H H
Epinephrine H
(major hormone of HO C C N
Antagonistic effects Cholinergic
adrenal medulla)
CH3 Smooth receptors
OH H
muscle cell
Figure 9.8 The catecholamine family of
molecules. Catecholamines are derived from the amino acid
tyrosine, and include both neurotransmitters (dopamine and
ACh
norepinephrine) and a hormone (epinephrine). Notice that
epinephrine has an additional methyl (CH3) group compared to
norepinephrine.

Axon of Parasympathetic
Neuron Synaptic vesicle
adrenergic receptor, a drug may either promote or inhibit the with acetylcholine (Ach)
adrenergic effect. Also, by using these selective compounds, (b)
it has been possible to determine which subtype of adrenergic
receptor is present in each organ (table 9.5).
Figure 9.9 Sympathetic and parasympathetic axons
release different neurotransmitters. (a) The axons of
All adrenergic receptors act via G-proteins. The action of
autonomic neurons have varicosities that form synapses en
G-proteins was described in chapter 7, and can be reviewed
passant with the target cells. (b) In general, sympathetic axons
by reference to figure. 7.27 and table 7.6. In short, the bind-
release norepinephrine, which binds to its adrenergic receptors,
ing of epinephrine and norepinephrine to their receptors
while parasympathetic neurons release acetylcholine, which
causes the group of three G-proteins (designated α, β, and γ)
binds to its cholinergic receptors (discussed in chapter 7). In most
to dissociate into an α subunit and a βγ complex. In differ-
cases, these two neurotransmitters elicit antagonistic responses
ent cases, either the α subunit or the βγ complex causes the
from smooth muscles.
opening or closing of an ion channel in the plasma mem-
brane, or the activation of an enzyme in the membrane. This
begins the sequence of events that culminates in the effects
of epinephrine and norepinephrine on the target cells.

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 The Autonomic Ner vous System 251

Table 9.5 | Selected Adrenergic Effects in Different Organs

Organ Adrenergic Effects of Sympathoadrenal System Adrenergic Receptor

Eye Contraction of radial fibers of the iris dilates the pupils α1

Heart Increase in heart rate and contraction strength β1 primarily

Skin and visceral vessels Arterioles constrict due to smooth muscle contraction α1

Skeletal muscle vessels Arterioles constrict due to sympathetic nerve activity α1

Arterioles dilate due to hormone epinephrine β2

Lungs Bronchioles (airways) dilate due to smooth muscle relaxation β2

Stomach and intestine Contraction of sphincters slows passage of food α1

Liver Glycogenolysis and secretion of glucose α1, β2

Source: Simplified from table 6-1, pp. 110–111, of Goodman and Gilman’s The Pharmacological Basis of Therapeutics. Ninth edition. J.E. Hardman et al., eds. 1996. McGraw-Hill.

All subtypes of beta receptors produce their effects by sympathetic division produces an increase in cardiac pump-
stimulating the production of cyclic AMP within the target ing (a β1 effect), vasoconstriction and thus reduced blood
cells. The response of a target cell when norepinephrine flow to the visceral organs (an α1 effect), dilation of pulmo-
binds to the α1 receptors is mediated by a different second- nary bronchioles (a β2 effect), and so on, preparing the body
messenger system—a rise in the cytoplasmic concentration for physical exertion (fig. 9.10).
of Ca2+. This Ca2+ second-messenger system is similar, in A drug that binds to the receptors for a neurotransmitter
many ways, to the cAMP system and is discussed together and that promotes the processes that are stimulated by that
with endocrine regulation in chapter 11 (see fig. 11.10). It neurotransmitter is said to be an agonist of that neurotrans-
should be remembered that each of the intracellular changes mitter. A drug that blocks the action of a neurotransmitter,
following the binding of norepinephrine to its receptor ulti-
mately results in the characteristic response of the tissue to
the neurotransmitter.
The physiology of α2-adrenergic receptors is complex. CLINICAL APPLICATION
These receptors are located on presynaptic axon terminals,
and when stimulated, cause a decreased release of norepine- Many people with hypertension were once treated with a beta-
phrine. This may represent a form of negative feedback control. blocking drug known as propranolol. This drug blocks β1
On the other hand, vascular smooth muscle cells also have receptors, which are located in the heart, and thus produces
α2-adrenergic receptors on the postsynaptic membrane, where the desired effect of lowering the cardiac rate and blood pres-
they can be activated to produce vasoconstriction. This action sure. Propranolol, however, also blocks β2 receptors, which
would cause a rise in blood pressure. However, drugs that are located in the bronchioles of the lungs. This reduces the
activate α2-adrenergic receptors are used to lower blood pres- bronchodilation effect of epinephrine, producing bronchocon-
sure. This is because they stimulate presynaptic α2-adrenergic striction and asthma in susceptible people. A more selective β1
receptors in the brain, and this somehow reduces the activity antagonist, atenolol, is now used instead to slow the cardiac
of the entire sympathetic nervous system. rate and lower blood pressure. At one time, asthmatics inhaled
A review of table 9.5 reveals certain generalities about the an epinephrine spray, which stimulates β1 receptors in the
actions of adrenergic receptors. The stimulation of α1-adrenergic heart as well as β2 receptors in the airways. Now, drugs such
receptors consistently causes contraction of smooth muscles. as terbutaline that more selectively function as β2 agonists are
We can thus state that the vasoconstrictor effect of sympa- commonly used.
thetic nerves always results from the activation of alpha- Drugs such as phenylephrine, which function as α1 ago-
adrenergic receptors. The effects of beta-adrenergic activation nists, are often included in cold medicines because they pro-
are more diverse; stimulation of beta-adrenergic receptors pro- mote vasoconstriction in the nasal mucosa. Clonidine is a drug
motes the relaxation of smooth muscles (in the digestive tract, that selectively stimulates α2 receptors located on neurons in
bronchioles, and uterus, for example) but increases the force the brain. As a consequence of its action, clonidine suppresses
of contraction of cardiac muscle and promotes an increase in the activation of the sympathoadrenal system and thereby
cardiac rate. helps to lower blood pressure. This drug is also helpful in treat-
The diverse effects of epinephrine and norepineph- ing patients with an addiction to opiates who are experiencing
rine can be understood in terms of the “fight-or-flight” withdrawal symptoms.
theme. Adrenergic stimulation wrought by activation of the

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 252 Chapter 9

Parasympathetic division Sympathetic division

Preganglionic
neurons

Nicotinic
ACh ACh receptors

Postganglionic
neurons

ACh Norepinephrine

Stimulates Stimulates Stimulates Stimulates

muscarinic ACh α1-adrenergic β1-adrenergic β2-adrenergic
receptors receptors receptors receptors

Parasympathetic Vasoconstriction in Increased Dilation of

nerve effects viscera and skin heart rate and bronchioles
contractility of lung

Figure 9.10 Receptors involved in autonomic regulation. Acetylcholine is released by all preganglionic neurons and
stimulates postganglionic neurons by means of nicotinic ACh receptors. Postganglionic parasympathetic axons regulate their target
organs through muscarinic ACh receptors. Postganglionic sympathetic axons provide adrenergic regulation of their target organs by
binding of norepinephrine to α1-, β1-, and β2-adrenergic receptors.

by contrast, is said to be an antagonist. The use of specific Responses to Cholinergic

drugs that selectively stimulate or block α1, α2, β1, and β2
receptors has proven extremely useful in many medical Stimulation
applications (see the Clinical Application box on page 251). All somatic motor neurons, all preganglionic neurons
(sympathetic and parasympathetic), and most postgan-
glionic parasympathetic neurons are cholinergic—they
release acetylcholine (ACh) as a neurotransmitter. The
Case Investigation CLUES effects of ACh released by somatic motor neurons and by
preganglionic autonomic neurons are always excitatory.
Kathy used her inhaler for her asthma, and had
The effects of ACh released by postganglionic parasym-
an elevated pulse rate and blood pressure in the laboratory
pathetic axons are usually excitatory, but in some cases
following her physiology exam.
they are inhibitory. For example, the cholinergic effect
■ How might her inhaler for asthma contribute to these of the postganglionic parasympathetic axons innervating
elevated measurements? the heart (a part of the vagus nerve) slows the heart rate.
■ How might her exam have contributed to these It is useful to remember that, in general, the effects of
elevated measurements? parasympathetic innervation are opposite to the effects of
sympathetic innervation.

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 The Autonomic Ner vous System 253

The effects of ACh in an organ depend on the nature of different membrane enzymes. As a result, their effects can be
the cholinergic receptor (fig. 9.11). As may be recalled from either excitatory or inhibitory (fig. 9.11).
chapter 7, there are two types of cholinergic receptors—nicotinic Scientists have identified five different subtypes of musca-
and muscarinic. Nicotine (derived from the tobacco plant), as rinic receptors (M1 through M5; table 9.6). Some of these cause
well as ACh, stimulates the nicotinic ACh receptors. These are contraction of smooth muscles and secretion of glands, while
located in the neuromuscular junction of skeletal muscle fibers
and in the autonomic ganglia. Nicotinic receptors are thus stim- CLINICAL APPLICATION
ulated by ACh released by somatic motor neurons and by pre-
ganglionic autonomic neurons. Muscarine (derived from some The muscarinic effects of ACh are specifically inhibited by the
poisonous mushrooms), as well as ACh, stimulates the ACh drug atropine, derived from the deadly nightshade plant
receptors in the visceral organs. Muscarinic receptors are thus (Atropa belladonna). Indeed, extracts of this plant were used
stimulated by ACh released by postganglionic parasympathetic by women during the Middle Ages to dilate their pupils
axons to produce the parasympathetic effects. Nicotinic and (atropine inhibits parasympathetic stimulation of the iris). This
muscarinic receptors are further distinguished by the action of was thought to enhance their beauty (in Italian, bella = beauti-
the drugs curare (tubocurarine), which specifically blocks the ful, donna = woman). Atropine is used clinically today to dilate
nicotinic ACh receptors, and atropine (or belladonna), which pupils during eye examinations, to reduce secretions of the
specifically blocks the muscarinic ACh receptors. respiratory tract prior to general anesthesia, to inhibit spas-
As described in chapter 7, the nicotinic ACh receptors modic contractions of the lower digestive tract, and to inhibit
are ligand-gated ion channels. That is, binding to ACh causes stomach acid secretion in a person with gastritis. Atropine is
the ion channel to open within the receptor protein. This also given intramuscularly to treat exposure to nerve gas,
allows Na+ to diffuse inward and K+ to diffuse outward. which inhibits acetylcholinesterase and thereby increases syn-
However, the Na+ gradient is steeper than the K+ gradient, aptic transmission at both nicotinic and muscarinic ACh recep-
and so the net effect is a depolarization. As a result, nico- tors. Atropine blocks the muscarinic effects of nerve gas,
tinic ACh receptors are always excitatory. In contrast, mus- which include increased mucous secretions of the respiratory
carinic ACh receptors are coupled to G-proteins, which can tract and muscular spasms in the pulmonary airways.
then close or open different membrane channels and activate

Nicotinic ACh Muscarinic ACh

receptors receptors

Postsynaptic membrane of • Produces parasympathetic nerve effects in

• All autonomic ganglia the heart, smooth muscles, and glands
• All neuromuscular junctions • G-protein-coupled receptors (receptors
• Some CNS pathways influence ion channels by means of G-proteins)

Na+ Na+ or Ca2+

ACh ACh ACh

Ligand-gated channels
(ion channels are part
of receptor) αβ αβ
γ γ
K+
K+ K+

Depolarization Hyperpolarization Depolarization

(K+ channels (K+ channels

opened) closed)

Excitation Inhibition Excitation

Produces slower Causes smooth muscles of the

heart rate digestive tract to contract

Figure 9.11 Comparison of nicotinic and muscarinic acetylcholine receptors. Nicotinic receptors are ligand-gated,
meaning that the ion channel (which runs through the receptor) is opened by binding to the neurotransmitter molecule (the ligand). The
muscarinic ACh receptors are G-protein-coupled receptors, meaning that the binding of ACh to its receptor indirectly opens or closes ion
channels through the action of G-proteins.

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 254 Chapter 9

Table 9.6 | Cholinergic Receptors and Responses to Acetylcholine

Receptor Tissue Response Mechanisms
Nicotinic Skeletal muscle Depolarization, producing action potentials ACh opens cation channel in receptor
and muscle contraction

Nicotinic Autonomic ganglia Depolarization, causing activation of ACh opens cation channel in receptor
postganglionic neurons

Muscarinic (M3, M5) Smooth muscle, Depolarization and contraction of smooth ACh activates G-protein coupled receptor, opening
glands muscle, secretion of glands Ca2+ channels and increasing cytosolic Ca2+

Muscarinic (M2) Heart Hyperpolarization, slowing rate of ACh activates G-protein coupled receptor, opening
spontaneous depolarization channels for K+

Source: Simplified from table 6-2, p. 119 of Goodman and Gilman’s The Pharmacological Basis of Therapeutics. Ninth edition. J.E. Hardman et al., eds. 1996 and
table 6-3, p. 156 of the Eleventh edition, 2006. McGraw-Hill.

others cause the inhibition that results in a slowing of the Studies suggest that nitric oxide is not stored in synaptic
heart rate. These actions are mediated by second-messenger vesicles, as are other neurotransmitters, but instead is pro-
systems that will be discussed in more detail in conjunction duced immediately when Ca2+ enters the axon terminal in
with hormone action in chapter 11, section 11.2. response to action potentials. This Ca2+ indirectly activates
nitric oxide synthetase, the enzyme that forms nitric oxide
from the amino acid L-arginine. Nitric oxide then diffuses
across the synaptic cleft and promotes relaxation of the
postsynaptic smooth muscle cells.
Nitric oxide can produce relaxation of smooth muscles
Case Investigation CLUES in many organs, including the stomach, small intestine, large
Kathy had a headache, dry mouth, and dilated intestine, and urinary bladder. There is some controversy,
pupils following her use of various drugs on a frog heart. however, about whether the nitric oxide functions as a neu-
■ Which drug likely produced these effects? rotransmitter in each case. It has been argued that, in some
■ How did the drug work to cause these symptoms? cases, nitric oxide could be produced in the organ itself in
response to autonomic stimulation. The fact that different tis-
sues, such as the endothelium of blood vessels, can produce
nitric oxide lends support to this argument. Indeed, nitric
oxide is a member of a class of local tissue regulatory mol-
Other Autonomic ecules called paracrine regulators (chapter 11, section 11.7).
Neurotransmitters Regulation can therefore be a complex process involving the
interacting effects of different neurotransmitters, hormones,
Certain postganglionic autonomic axons produce their
and paracrine regulators.
effects through mechanisms that do not involve either nor-
epinephrine or acetylcholine. This can be demonstrated
experimentally by the inability of drugs that block adrenergic
and cholinergic effects from inhibiting the actions of those
autonomic axons. These axons, consequently, have been Organs with Dual Innervation
termed “nonadrenergic, noncholinergic fibers.” Proposed Most visceral organs receive dual innervation—they are
neurotransmitters for these axons include ATP, a polypep- innervated by both sympathetic and parasympathetic fibers.
tide called vasoactive intestinal peptide (VIP), and nitric In this condition, the effects of the two divisions of the auto-
oxide (NO). nomic system may be antagonistic, complementary, or coop-
The nonadrenergic, noncholinergic parasympathetic erative (table 9.7).
axons that innervate the blood vessels of the penis cause
the smooth muscles of these vessels to relax, thereby pro-
ducing vasodilation and a consequent erection of the penis Antagonistic Effects
(chapter 20, fig. 20.21). These parasympathetic axons The effects of sympathetic and parasympathetic innervation
have been shown to use the gas nitric oxide (chapter 7, of the pacemaker region of the heart is the best example of the
section  7.6) as their neurotransmitter. In a similar man- antagonism of these two systems. In this case, sympathetic
ner, nitric oxide appears to function as the autonomic neu- and parasympathetic fibers innervate the same cells. Adren-
rotransmitter that causes vasodilation of cerebral arteries. ergic stimulation from sympathetic fibers increases the heart

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