162 CHAPTER 9 ■ Nerve Tissue & the Nervous System

FIGURE 9–1 The general organization of the nervous system.

Anatomically the nervous system is divided into the CNS and PNS,
Cerebrum which have thewjor components shown in the diagram.
Central
Cerebellum nervous Functionally the nervous system consists of the following:
Spinal system (CNS)
cord 1. Sensory division (afferent)
A. Somatic—sensory input perceived consciously (eg, from
eyes ears, skin, and musculoskeletal structures)

Cranial
B. Visceral—sensory input not perceived consciously (eg,
nerves from internal organs and cardiovascular
Neural groove structures)
Peripheral
Spinal nervous 2. Motor division (efferent)
nerves system (PNS)
A. Somatic—motor output controlled consciously or volun-
Neural
Ganglia tarily (eg, by skeletal muscle effectors) crest
Neural folds
Autonomic—motor output not controlled consciously (eg,
B. Notochord
by heart or gland effectors)
The autonomic motor nerves, comprising what is often called
the autonomic nervous system
1 Neural (ANS),
folds all have
and neural pathways
groove form involving
from the
two neurons: a preganglionic neural plate.
neuron with the cell body in the CNS
and a postganglionic neuron with the cell body in a ganglion. The
ANS has two divisions: (1) The parasympathetic
Neural groove division, with its
ganglia within or near the effector organs, maintains normal body
homeostasis. (2) The sympathetic division has its ganglia close to
the CNS and controls the body’s responses during emergencies and
excitement. ANS components located in the wall of the digestive
tract are sometimes referred to as the enteric nervous system.

2 Neural folds elevate and approach one

FIGURE 9–2 Neurulation in the early embryo. another.

Neural groove Neural groove

Neural
Ectoderm crest
Neural cells
crest
Neural folds
Notochord

Neural folds and neural groove form 3 As neural folds prepare to fuse and form
1 the neural tube and dorsal epidermis,
from the neural plate. neural crest cells loosen and become
mesenchymal.
Neural groove
Neural tube

Neural
crest
cells Developing
epidermis

2 Neural folds elevate and approach one

another. 4 The mass of neural crest cells initially
lies atop the newly formed neural tube.
Neural groove
Stages in the process of neurulation, by which cells of the CNS converting the groove into the neural tube (4), which is large at
and PNS are produced, are shown in diagrammatic crossNeural sections the cranial end of the embryo and much narrower caudally. The
of a 3- and 4-week human embryo with the extraembryonic
Ectoderm crestmem- neural tube will give rise to the entire CNS.
branes removed. Under an inductive influence from the medial cells As the neural tube detaches from the now overlying ectoderm,
notochord, the overlying layer of ectodermal cells thickens as a many cells separate from it and produce a mass of mesenchymal
bending neural plate, with a medial neural groove and lateral cells called the neural crest. Located initially above the neural
neural folds (1). All other ectoderm will become epidermis. The tube, neural crest cells immediately begin migrating laterally. Cell
plate bends further, making the neural folds and groove more derived from the neural crest will form all components of the PNS
prominent (2).
3 AsTheneural
neuralfolds
folds rise and
prepare to fuse
fuse at
and midline (3),
theform and also contribute to certain non-neural tissues.
the neural tube and dorsal epidermis,
neural crest cells loosen and become
mesenchymal.
 Neurons 163

the neural tube. Cells of this tube give rise to the entire CNS, stimuli from receptors throughout the body. Motor neu-
including neurons and most glial cells. rons are efferent, sending impulses to effector organs such

C H A P T E R
As the folds fuse and the neural tube separates from the as muscle fibers and glands. Somatic motor nerves are under
now overlying surface ectoderm that will form epidermis, a voluntary control and typically innervate skeletal muscle;
large population of developmentally important cells, the neu- autonomic motor nerves control the involuntary or uncon-
ral crest, separates from the neuroepithelium and becomes scious activities of glands, cardiac muscle, and most smooth
mesenchymal. Neural crest cells migrate extensively and dif- muscle.
ferentiate as all the cells of the PNS, as well as a number of Interneurons establish relationships among other neu-

9
other non-neuronal cell types. rons, forming complex functional networks or circuits in

Nerve Tissue & the Nervous System ■ Neurons

the CNS. Interneurons are either multipolar or anaxonic and
comprise 99% of all neurons in adults.
› NEURONS In the CNS most neuronal perikarya occur in the gray
matter, with their axons concentrated in the white matter.
The functional unit in both the CNS and PNS is the neuron. These terms refer to the general appearance of unstained
Some neuronal components have special names, such as “neu- CNS tissue caused in part by the different densities of nerve
rolemma” for the cell membrane. Most neurons have three cell bodies. In the PNS cell bodies are found in ganglia and in
main parts (Figure 9–3): some sensory regions, such as the olfactory mucosa, and axons
■ The cell body (also called the perikaryon or soma), are bundled in nerves.
which contains the nucleus and most of the cell’s organ-
elles and serves as the synthetic or trophic center for the
entire neuron. › › MEDICAL APPLICATION
■ The dendrites, which are the numerous elongated pro- Parkinson disease is a slowly progressing disorder affecting
cesses extending from the perikaryon and specialized to muscular activity characterized by tremors, reduced activity
receive stimuli from other neurons at unique sites called of the facial muscles, loss of balance, and postural stiffness.
synapses. It is caused by gradual loss by apoptosis of dopamine-
■ The axon (Gr. axon, axis), which is a single long process producing neurons whose cell bodies lie within the nuclei
ending at synapses specialized to generate and conduct of the CNS substantia nigra. Parkinson disease is treated
nerve impulses to other cells (eg, nerve, muscle, and with L-dopa (L-3,4-dihydroxyphenylalanine), a precursor of
gland cells). Axons may also receive information from dopamine that augments the declining production of this
other neurons, information that mainly modifies the neurotransmitter.
transmission of action potentials to those neurons.
Neurons and their processes or “nerve fibers” are variable
in size and shape. Cell bodies can be very large, measuring up Cell Body (Perikaryon or Soma)
to 150 μm in diameter. Other neurons, such as those in the The neuronal cell body contains the nucleus and surround-
cerebellar granular layer, are among the body’s smallest cells. ing cytoplasm, exclusive of the cell processes (Figure 9–3).
Neurons can be classified according to the number of pro- It acts as a trophic center, producing most cytoplasm for the
cesses extending from the cell body (Figure 9–4): processes. Most cell bodies are in contact with a great number
of nerve endings conveying excitatory or inhibitory stimuli
■ Multipolar neurons, each with one axon and two or
generated in other neurons. A typical neuron has an unusu-
more dendrites, are the most common.
ally large, euchromatic nucleus with a prominent nucleolus,
■ Bipolar neurons, with one dendrite and one axon,
indicating intense synthetic activity.
comprise the sensory neurons of the retina, the olfactory
Cytoplasm of perikarya often contains numerous free
epithelium, and the inner ear.
polyribosomes and highly developed RER, indicating active
■ Unipolar or pseudounipolar neurons, which include
production of both cytoskeletal proteins and proteins for
all other sensory neurons, each have a single process that
transport and secretion. Histologically these regions with
bifurcates close to the perikaryon, with the longer branch
concentrated RER and other polysomes are basophilic and
extending to a peripheral ending and the other toward
are distinguished as chromatophilic substance (or Nissl
the CNS.
substance, Nissl bodies) (Figure 9–3). The amount of this
■ Anaxonic neurons, with many dendrites but no true
material varies with the type and functional state of the neu-
axon, do not produce action potentials, but regulate elec-
ron and is particularly abundant in large nerve cells such
trical changes of adjacent CNS neurons.
as motor neurons (Figure 9–3b). The Golgi apparatus is
Because the fine processes emerging from cell bodies are located only in the cell body, but mitochondria can be found
seldom seen in sections of nervous tissue, it is difficult to clas- throughout the cell and are usually abundant in the axon
sify neurons structurally by microscopic inspection. terminals.
Nervous components can also be subdivided function- In both perikarya and processes microtubules, actin
ally (Figure 9–1). Sensory neurons are afferent, receiving filaments and intermediate filaments are abundant, with the
164 CHAPTER 9 ■ Nerve Tissue & the Nervous System

FIGURE 9–3 Structures of a typical neuron.

G
D
Dendrites

Nucleolus NS
Nucleus

Cell body N
Chromatophilic
(Nissl) substance
Axon hillock

Axoplasm
Axolemma AH
Neurofibrils

Axon (beneath Axon collateral

myelin sheath)

Neurolemmocyte

Neurofibril node

Myelin sheath
b
Telodendria
Synaptic knobs

Synaptic vesicles
containing
neurotransmitter

Synaptic cleft
Postsynaptic neuron
(or effector)
Synapse

(a) A “typical” neuron has three major parts: (1) The cell body
(also called the perikaryon or soma) is often large, with a large,
euchromatic nucleus and well-developed nucleolus. The cyto-
plasmic contains basophilic Nissl substance or Nissl bodies,
which are large masses of free polysomes and RER indicating
the cell’s high rate of protein synthesis. (2) Numerous short den-
drites extend from the perikaryon, receiving input from other
neurons. (3) A long axon carries impulses from the cell body and
is covered by a myelin sheath composed of other cells. The ends
of axons usually have many small branches (telodendria), each
of which ends in a knob-like structure that forms part of a func-
tional connection (synapse) with another neuron or other cell.
(b) Micrograph of a large motor neuron showing the large cell
body and nucleus (N), a long axon (A) emerging from an axon
hillock (AH), and several dendrites (D). Nissl substance (NS) can
be seen throughout the cell body and cytoskeletal elements can
be detected in the processes. Nuclei of scattered glial cells (G)
are seen among the surrounding tissue. (X100; H&E)
 Neurons 165

FIGURE 9–4 Structural classes of neurons.

C H A P T E R
Dendrites Cell body
Dendrite

Cell body Axon

9
b Bipolar neuron

Nerve Tissue & the Nervous System ■ Neurons

Axon
Dendrites

a Multipolar neuron

Axon

Peripheral process Central process

Cell body

Dendrites
Dendrites Cell body Single short process

c Unipolar neuron d Anaxonic neuron

Shown are the four main types of neurons, with short descriptions. neurons are unipolar or pseudounipolar. (d) Anaxonic neurons
(a) Most neurons, including all motor neurons and CNS interneu- of the CNS lack true axons and do not produce action potentials,
rons, are multipolar. (b) Bipolar neurons include sensory neurons but regulate local electrical changes of adjacent neurons.
of the retina, olfactory mucosa, and inner ear. (c) All other sensory

latter formed by unique protein subunits and called neurofila- and studied by confocal or electron microscopy. Dendritic
ments in this cell type. Cross-linked with certain fixatives and spines serve as the initial processing sites for synaptic signals
impregnated with silver stains, neurofilaments are also referred and occur in vast numbers, estimated to be on the order of 1014
to as neurofibrils by light microscopists. Some nerve cell bodies for cells of the human cerebral cortex. Dendritic spine mor-
also contain inclusions of pigmented material, such as lipofus- phology depends on actin filaments and changes continuously
cin, consisting of residual bodies left from lysosomal digestion. as synaptic connections on neurons are modified. Changes in
dendritic spines are of key importance in the constant changes
Dendrites of the neural plasticity that occurs during embryonic brain
development and underlies adaptation, learning, and memory
Dendrites (Gr. dendron, tree) are typically short, small pro-
postnatally.
cesses emerging and branching off the soma (Figure 9–3).
Usually covered with many synapses, dendrites are the principal
signal reception and processing sites on neurons. The large Axons
number and extensive arborization of dendrites allow a single neu- Most neurons have only one axon, typically longer than its
ron to receive and integrate signals from many other nerve cells. dendrites. Axonal processes vary in length and diameter
For example, up to 200,000 axonal endings can make func- according to the type of neuron. Axons of the motor neurons
tional contact with the dendrites of a single large Purkinje cell that innervate the foot muscles have lengths of nearly a meter;
of the cerebellum. large cell bodies are required to maintain these axons, which
Unlike axons, which maintain a nearly constant diameter, contain most of such neurons’ cytoplasm. The plasma mem-
dendrites become much thinner as they branch, with cyto- brane of the axon is often called the axolemma and its con-
skeletal elements predominating in these distal regions. In the tents are known as axoplasm.
CNS most synapses on dendrites occur on dendritic spines, Axons originate from a pyramid-shaped region of the
which are dynamic membrane protrusions along the small perikaryon called the axon hillock (Figure 9–3), just beyond
dendritic branches, visualized with silver staining (Figure 9–5) which the axolemma has concentrated ion channels that
166 CHAPTER 9 ■ Nerve Tissue & the Nervous System

injected into regions with axon terminals, its later distribution

FIGURE 9–5 Dendrites and dendritic spines.
throughout the neurons serving such regions can be deter-
mined histochemically.
Anterograde and retrograde transports both occur fairly
rapidly, at rates of 50-400 mm/d. A much slower anterograde
stream, moving only a few millimeters per day, involves move-
ment of the axonal cytoskeleton itself. This slow axonal trans-
port corresponds roughly to the rate of axon growth.
DS
D D Nerve Impulses
A nerve impulse, or an action potential, travels along
an axon like a spark moves along an explosive’s fuse. It is an
electrochemical process initiated at the axon hillock when
other impulses received at the cell body or dendrites meet a
D certain threshold. The action potential is propagated along
the axon as a wave of membrane depolarization produced by
CB
voltage-gated Na+ and K+ channels in the axolemma that
allow diffusion of these ions into and out of the axoplasm. The
extracellular compartment around all regions of the neuron is
The large Purkinje neuron in this silver-impregnated section of a very thin zone immediately outside the cell that is formed by
cerebellum has many dendrites (D) emerging from its cell body enclosing glial cells that also regulate its ionic contents.
(CB) and forming branches. The small dendritic branches each In unstimulated neurons, ATP-dependent Na-K pumps
have many tiny projecting dendritic spines (DS) spaced closely and other membrane proteins maintain an axoplasmic Na+
along their length, each of which is a site of a synapse with
concentration only one-tenth of that outside the cell and a K+
another neuron. Dendritic spines are highly dynamic, the num-
ber of synapses changing constantly. (X650; Silver stain) level many times greater than the extracellular concentration.
This produces a potential electrical difference across the axo-
lemma of about –65 mV, with the inside negative to the out-
side. This difference is the axon’s resting potential.
generate the action potential. At this initial segment of the
axon, the various excitatory and inhibitory stimuli impinging
on the neuron are algebraically summed, resulting in the deci- › › MEDICAL APPLICATION
sion to propagate—or not to propagate—a nerve impulse.
Most local anesthetics are low-molecular-weight molecules
Axons generally branch less profusely than dendrites,
that bind to the voltage-gated sodium channels of the axo-
but do undergo terminal arborization (Figure 9–3). Axons
lemma, interfering with sodium ion influx and, consequently,
of interneurons and some motor neurons also have major
inhibiting the action potential responsible for the nerve
branches called collaterals that end at smaller branches with
impulse.
synapses influencing the activity of many other neurons. Each
small axonal branch ends with a dilation called a terminal
bouton (Fr. bouton, button) that contacts another neuron or When the threshold for triggering an impulse is met,
non-nerve cell at a synapse to initiate an impulse in that cell. channels at the axon’s initial segment open and allow a very
Axoplasm contains mitochondria, microtubules, neuro- rapid influx of extracellular Na+ that makes the axoplasm
filaments, and transport vesicles, but very few polyribosomes positive in relation to the extracellular environment and shifts
or cisternae of RER, features that emphasize the dependence (depolarizes) the resting potential from negative to positive,
of axoplasm on the perikaryon. If an axon is severed from its to +30 mV. Immediately after the membrane depolarization,
cell body, its distal part quickly degenerates and undergoes the voltage-gated Na+ channels close and those for K+ open,
phagocytosis. which rapidly returns the membrane to its resting potential.
Lively bidirectional transport of molecules large and This cycle of events occurs in less than 1 millisecond.
small occurs within axons. Organelles and macromolecules Depolarization stimulates adjacent portions of the axo-
synthesized in the cell body move by anterograde trans- lemma to depolarize and return immediately to the resting
port along axonal microtubules via kinesin from the peri- potential, which causes a nerve impulse, or wave of depolariza-
karyon to the synaptic terminals. Retrograde transport in tion, to move rapidly along the axon. After a refractory period
the opposite direction along microtubules via dynein carries also measured in milliseconds, the neuron is ready to repeat
certain other macromolecules, such as material taken up by this process and generate another action potential. Impulses
endocytosis (including viruses and toxins), from the periph- arriving at the synaptic nerve endings promote the discharge
ery to the cell body. Retrograde transport can be used to study of stored neurotransmitter that stimulates or inhibits action
the pathways of neurons: if peroxidase or another marker is potentials in another neuron or a non-neural cell.
 Neurons 167

Synaptic Communication ■ The postsynaptic cell membrane contains recep-

tors for the neurotransmitter, and ion channels or other

C H A P T E R
Synapses (Gr. synapsis, union) are sites where nerve impulses
mechanisms to initiate a new impulse.
are transmitted from one neuron to another, or from neurons
and other effector cells. The structure of a synapse (Figure 9–6)
■ A 20- to 30-nm-wide intercellular space called the syn-
aptic cleft separates these presynaptic and postsynaptic
ensures that transmission is unidirectional. Synapses convert
membranes.
an electrical signal (nerve impulse) from the presynaptic
cell into a chemical signal that affects the postsynaptic cell. At the presynaptic region the nerve impulse briefly opens
Most synapses act by releasing neurotransmitters, which calcium channels, promoting a Ca2+ influx that triggers neu-

9
are usually small molecules that bind specific receptor pro- rotransmitter release by exocytosis or similar mechanisms.

Nerve Tissue & the Nervous System ■ Neurons

teins to either open or close ion channels or initiate second- Immediately the released neurotransmitter molecules diffuse
messenger cascades. A synapse (Figure 9–6a) has the following across the synaptic cleft and bind receptors at the postsynap-
components: tic region. This produces either an excitatory or an inhibitory
effect at the postsynaptic membrane, as follows:
■ The presynaptic axon terminal (terminal bouton)
contains mitochondria and numerous synaptic vesicles ■ Neurotransmitters from excitatory synapses cause
from which neurotransmitter is released by exocytosis. postsynaptic Na+ channels to open, and the resulting Na+

FIGURE 9–6 Major components of a synapse.

Nerve impulse
Axon of presynaptic neuron

Mitochondria

Calcium Microtubules
(Ca2+) ions of cytoskeleton
T1
Voltage-regulated Synaptic vesicles
calcium (Ca2+) containing
channel acetylcholine (ACh) D
Synaptic
cleft

Acetylcholine
Acetylcholine binds T2
to receptor protein, Postsynaptic
causing ion gates Sodium membrane
to open (Na+) ions Receptor protein
a Postsynaptic neuron b

(a) Diagram showing a synapse releasing neurotransmitters (b) The TEM shows a large presynaptic terminal (T1) filled with
by exocytosis from the terminal bouton. Presynaptic terminals synaptic vesicles and asymmetric electron-dense regions around
always contain a large number of synaptic vesicles containing 20- to 30-nm-wide synaptic clefts (arrows). The postsynaptic mem-
neurotransmitters, numerous mitochondria, and smooth ER as a brane contains the neurotransmitter receptors and mechanisms to
source of new membrane. Some neurotransmitters are synthesized initiate an impulse at the postsynaptic neuron. The postsynaptic
in the cell body and then transported in vesicles to the presynaptic membrane on the right is part of a dendrite (D), associated with
terminal. Upon arrival of a nerve impulse, voltage-regulated Ca2+ fewer vesicles of any kind, showing this to be an axodendritic syn-
channels permit Ca2+ entry, which triggers neurotransmitter release apse. On the left is another presynaptic terminal (T2), suggesting an
into the synaptic cleft. Excess membrane accumulating at the axoaxonic synapse with a role in modulating activity of the other
presynaptic region as a result of exocytosis is recycled by clathrin- terminal. (X35,000)
mediated endocytosis, which is not depicted here.
168 CHAPTER 9 ■ Nerve Tissue & the Nervous System

influx initiates a depolarization wave in the postsynaptic larger blood vessels, the CNS has only a very small amount of
neuron or effector cell as just described. connective tissue and collagen. Glial cells substitute for cells
■ At inhibitory synapses neurotransmitters open Cl– of connective tissue in some respects, supporting neurons and
or other anion channels, causing influx of anions and creating immediately around those cells microenvironments
hyperpolarization of the postsynaptic cell, making its that are optimal for neuronal activity. The fibrous intercellular
membrane potential more negative and more resistant to network of CNS tissue superficially resembles collagen by light
depolarization. microscopy, but is actually the network of fine cellular pro-
cesses emerging from neurons and glial cells. Such processes
Interplay between excitatory and inhibitory effects on post-
are collectively called the neuropil (Figure 9–8).
synaptic cells allows synapses to process neuronal input and
There are six major kinds of glial cells, as shown schematically
fine-tune the reaction of the effector cell. Impulses passing from
in Figure 9–9, four in the CNS and two in the PNS. Their main
presynaptic neurons to postsynaptic cells are usually modified
functions, locations, and origins are summarized in Table 9–2.
at the synapse by similar connections there with other neurons
(Figure 9–6b). The response in postsynaptic neurons is deter- Oligodendrocytes
mined by the summation of activity at hundreds of synapses on
that cell. Three common morphological types of synapses occur Oligodendrocytes (Gr. oligos, small, few + dendron, tree +
between neurons of the CNS and are shown in Figure 9–7. kytos, cell) extend many processes, each of which becomes
The chemical transmitter used at neuromuscular junctions sheetlike and wraps repeatedly around a portion of a nearby
and some synapses of the CNS is acetylcholine. Within the CNS axon (Figure 9–9a). During this wrapping most cyto-
CNS other major categories of neurotransmitters include the plasm gradually moves out of the growing extension, leav-
following: ing multiple compacted layers of cell membrane collectively
termed myelin. An axon’s full length is covered by the action
■ Certain amino acids (often modified), such as gluta- of many oligodendrocytes. The resulting myelin sheath elec-
mate and γ-aminobutyrate (GABA) trically insulates the axon and facilitates rapid transmission
■ Monoamines, such as serotonin (5-hydroxytryptamine of nerve impulses. Found only in the CNS oligodendrocytes
or 5-HT) and catecholamines, such as dopamine, all of are the predominant glial cells in white matter, which is white
which are synthesized from amino acids because of the lipid concentrated in the wrapped membrane
■ Small polypeptides, such as endorphins and substance P. sheaths. The processes and sheaths are not visible by routine
Important actions of these and other common neurotrans- light microscope staining, in which oligodendrocytes usu-
mitters are summarized in Table 9–1. Different receptors and ally appear as small cells with rounded, condensed nuclei and
second messenger systems often occur for the same transmit- unstained cytoplasm (Figure 9–8a).
ter, greatly multiplying the possible effects of these molecules.
Astrocytes
After their release, transmitters are removed quickly by enzy-
matic breakdown, by glial activity, or by endocytotic recycling Also unique to the CNS astrocytes (Gr. astro-, star + kytos)
involving presynaptic membrane receptors. have a large number of long radiating, branching processes
(Figures 9–9a and 9–10). Proximal regions of the astrocytic
processes are reinforced with bundles of intermediate filaments
› › MEDICAL APPLICATION made of glial fibrillary acid protein (GFAP), which serves as
Levels of neurotransmitters in the synaptic cleft and available a unique marker for this glial cell. Distally the processes lack
for binding postsynaptic receptors are normally regulated GFAP, are not readily seen by microscopy, and form a vast net-
by several local mechanisms. Selective serotonin reuptake work of delicate terminals contacting synapses and other struc-
inhibitors (SSRIs), a widely used class of drugs for treat- tures. Terminal processes of a single astrocyte typically occupy
ment of depression and anxiety disorders, were designed to a large volume and associate with over a million synaptic sites.
augment levels of this neurotransmitter at the postsynaptic Astrocytes originate from progenitor cells in the embry-
membrane of serotonergic CNS synapses by specifically onic neural tube and are by far the most numerous glial cells
inhibiting its reuptake at the presynaptic membrane. of the brain, as well as the most diverse structurally and func-
tionally. Fibrous astrocytes, with long delicate processes, are
abundant in white matter; those with many shorter processes

› GLIAL CELLS & NEURONAL ACTIVITY are called protoplasmic astrocytes and predominate in the
gray matter. The highly variable and dynamic processes medi-
Glial cells support neuronal survival and activities, and are ate most of these cells’ many functions.
10 times more abundant than neurons in the mammalian
brain. Like neurons most glial cells develop from progenitor › › MEDICAL APPLICATION
cells of the embryonic neural plate. In the CNS glial cells sur-
Most brain tumors are astrocytomas derived from fibrous
round both the neuronal cell bodies, which are often larger
astrocytes. These are distinguished pathologically by their
than the glial cells, and the processes of axons and dendrites
expression of GFAP.
occupying the spaces between neurons. Except around the
 Glial Cells & Neuronal Activity 169

FIGURE 9–7 Types of synapses.

C H A P T E R
Axosomatic synapse Axodendritic synapse Axoaxonic synapse

Axons
Axon Axon
Dendrite

9
Nerve Tissue & the Nervous System ■ Glial Cells & Neuronal Activity
Dendritic spine
Cell body

Dendrites

Axodendritic synapse
Axosomatic
synapse

Cell body
Axon hillock Axon

Axoaxonic synapse

Terminal arborizations

The diagrams show three common morphologic types of synapses. All three morphologic types of synapses have the features of
Branched axon terminals usually associate with and transmit a all true synapses: a presynaptic axon terminal that releases a
nerve impulse to another neuron’s cell body (or soma) or a den- transmitter; a postsynaptic cell membrane with receptors for the
dritic spine. These types of connections are termed an axosomatic transmitter; and an intervening synaptic cleft.
synapse and an axodendritic synapse, respectively. Less fre- Synaptic structure usually cannot be resolved by light micros-
quently, an axon terminal forms a synapse with an axon terminal of copy, although components such as dendritic spines may be
another neuron; such an axoaxonic synapse functions to modu- shown with special techniques (Figure 9–5).
late synaptic activity in the other two types.
170 CHAPTER 9 ■ Nerve Tissue & the Nervous System

TABLE 9–1 Common neurotransmitters and their actions.

Neurotransmitter Description/Action

ACETYLCHOLINE (ACh)
CH3 O Chemical structure significantly different from that of other neurotransmitters; active in
CNS and in both somatic and autonomic parts of PNS; binds to ACh receptors (cholinergic
H3 C N+ CH2 CH2 O C CH3 receptors) in PNS to open ion channels in postsynaptic membrane and stimulate muscle
contraction
CH3

AMINO ACIDS
O Molecules with both carboxyl (—COOH) and amine (—NH2) groups and various R groups;
act as important transmitters in the CNS
NH2 CH2 C
OH
R

Glutamate Excites activity in neurons to promote cognitive function in the brain (learning and memory);
most common neurotransmitter in the brain; opens Na+ channels
Gamma-aminobutyric acid (GABA) Synthesized from glutamate; primary inhibitory neurotransmitter in the brain; also influences
muscle tone; opens or closes various ion channels
Glycine Inhibits activity between neurons in the CNS, including retina; opens Cl– channels
MONOAMINES
OH Aromatic ring Molecules synthesized from an amino acid by removing the carboxyl group and retaining the
single amine group; also called biogenic amines
NH2 CH2 CH OH

OH

Serotonin or 5-hydroxytryptamine (5-HT) Has various functions in the brain related to sleep, appetite, cognition (learning, memory), and
mood; modulates actions of other neurotransmitters
Catecholamines A distinct group of monoamines
Dopamine Produces inhibitory activity in the brain; important roles in cognition (learning, memory),
motivation, behavior, and mood; opens K+ channels, closes Ca2+ channels
Norepinephrine (noradrenaline) Neurotransmitter of PNS (sympathetic division of autonomic nervous system) and specific
CNS regions
Epinephrine (adrenaline) Has various effects in the CNS, especially the spinal cord, thalamus, and hypothalamus
NEUROPEPTIDES

Tyr Gly Gly Phe Met

Small polypeptides act as signals to assist in and modulate communication among neurons in
the CNS
Enkephalin Helps regulate response to noxious and potentially harmful stimuli
Neuropeptide Y Involved in memory regulation and energy balance (increased food intake and decreased
physical activity)
Somatostatin Inhibits activities of neurons in specific brain areas
Substance P Assists with pain information transmission into the brain
Cholecystokinin (CCK) Stimulates neurons in the brain to help mediate satiation (fullness) and repress hunger
Beta-endorphin Prevents release of pain signals from neurons and fosters a feeling of well-being
Neurotensin Helps control and moderate the effects of dopamine
OTHERS
Adenosine Also part of a nucleotide, inhibits activities in certain CNS neurons
Nitric oxide Involved in learning and memory; relaxes muscle in the digestive tract; important for
relaxation of smooth muscle in blood vessels (vasodilation)
 Glial Cells & Neuronal Activity 171

FIGURE 9–8 Neurons, neuropil, and the common glial cells of the CNS.

C H A P T E R
G N
Np

9
N

Nerve Tissue & the Nervous System ■ Glial Cells & Neuronal Activity
G Np N
G G
G

a b

(a) Most neuronal cell bodies (N) in the CNS are larger than the those properties seen here. The other glial cells seen here similar in
much more numerous glial cells (G) that surround them. The vari- overall size, but with very little cytoplasm and more elongated or
ous types of glial cells and their relationships with neurons are oval nuclei, are mostly astrocytes. Routine H&E staining does not
difficult to distinguish by most routine light microscopic methods. allow neuropil to stand out well. (X200; H&E)
However, oligodendrocytes have condensed, rounded nuclei and (b) With the use of gold staining for neurofibrils, neuropil (Np) is
unstained cytoplasm due to very abundant Golgi complexes, more apparent. (X200; Gold chloride and hematoxylin)
which stain poorly and are very likely represented by the cells with

Functions attributed to astrocytes of various CNS regions ■ Extending fibrous processes with expanded perivas-
include the following: cular feet that cover capillary endothelial cells and
modulate blood flow and help move nutrients, wastes,
■ Extending processes that associate with or cover syn-
and other metabolites between neurons and capillaries
apses, affecting the formation, function, and plasticity of
(Figure 9–9a)
these structures
■ Regulating the extracellular ionic concentrations around
■ Forming a barrier layer of expanded protoplasmic pro-
cesses, called the glial limiting membrane, which lines
neurons, with particular importance in buffering extra-
the meninges at the external CNS surface
cellular K+ levels
■ Guiding and physically supporting movements and loca-
■ Filling tissue defects after CNS injury by proliferation to
form an astrocytic scar.
tions of differentiating neurons during CNS development

TABLE 9–2 Origin, location, and principal functions of neuroglial cells.

Glial Cell Type Origin Location Main Functions

Oligodendrocyte Neural tube CNS Myelin production, electrical insulation

Astrocyte Neural tube CNS Structural and metabolic support of
neurons, especially at synapses; repair
processes
Ependymal cell Neural tube Line ventricles and central Aid production and movement of CSF
canal of CNS
Microglia Bone marrow (monocytes) CNS Defense and immune-related activities
Schwann cell Neural crest Peripheral nerves Myelin production, electrical insulation
Satellite cells (of ganglia) Neural crest Peripheral ganglia Structural and metabolic support for
neuronal cell bodies
172 CHAPTER 9 ■ Nerve Tissue & the Nervous System

FIGURE 9–9 Glial cells of the CNS and PNS.

Functions of Astrocyte

1. Helps form the blood-brain barrier

2. Regulates interstitial fluid
composition
Astrocyte 3. Provides structural support and
organization to the central
Neuron nervous system (CNS)
Perivascular
feet 4. Assists with neuronal development
5. Replicates to occupy space of
dying neurons
Capillary

Myelinated axon Functions of Ependymal Cell

Ependymal
cell 1. Lines ventricles of brain and central
Myelin sheath (cut)
canal of spinal cord
2. Assists in production and circulation
Ventricle of
Oligodendrocyte brain of cerebrospinal fluid (CSF)

Functions of Microglial Cell

1. Phagocytic cells that move through

Functions of Oligodendrocyte
the CNS
Microglial 2. Protects the CNS by engulfing
1. Myelinates and insulates CNS axons cell
infectious agents and other
2. Allows faster action potential propagation along axons in the CNS potential harmful substances

(a)

Posterior root ganglion

Functions of Satellite Cell Satellite

cell

1. Electrically insulates PNS

cell bodies.
2. Regulates nutrient and
waste exchange for cell
bodies in ganglia

Functions of Neurolemmocyte Schwann cell

Axon
1. Surround and insulate PNS
axons and myelinate those
having large diameters
2. Allows for faster action
potential propagation along
an axon in the PNS

(b)

(a) There are four major kinds of glial cells in the CNS: oligoden- (b) Two glial cells occur in the PNS: Schwann cells (sometimes called
drocytes, astrocytes, ependymal cells, and microglial cells. The neurolemmocytes), which surround peripheral nerve fibers, and sat-
interrelationships and major functions of these cells are shown ellite cells, which surround the nerve cell bodies and are thus found
diagrammatically here. only in ganglia. Major functions of these cells are indicated.
 Glial Cells & Neuronal Activity 173

FIGURE 9–10 Astrocytes.

C H A P T E R
P PF

S A
C

9
Nerve Tissue & the Nervous System ■ Glial Cells & Neuronal Activity
A C
P A A
S

P PF
a b c

(a) Astrocytes are the most abundant glial cells of the CNS and are processes. The small pieces of other GFAP-positive processes in the
characterized by numerous cytoplasmic processes (P) radiating neuropil around this cell give an idea of the density of this glial cell
from the glial cell body or soma (S). Astrocytic processes are not and its processes in the CNS. Astrocytes form part of the blood-
seen with routine light microscope staining but are easily seen brain barrier (BBB) and help regulate entry of molecules and ions
after gold staining. Morphology of the processes allows astrocytes from blood into CNS tissue. Capillaries at the extreme upper right
to be classified as fibrous (relatively few and straight processes) or and lower left corners are enclosed by GFAP-positive perivascular
protoplasmic (numerous branching processes), but functional dif- feet (PF) at the ends of numerous astrocytic processes. (X500; Anti-
ferences between these types are not clear. (X500; Gold chloride) GFAP immunoperoxidase and hematoxylin counterstain)
(b) All astrocytic processes contain intermediate filaments of GFAP, (c) A length of capillary (C) is shown here completely covered by
and antibodies against this protein provide a simple method to silver-stained terminal processes extending from astrocytes (A).
stain these cells, as seen here in a fibrous astrocyte (A) and its (X400; Rio Hortega silver)

Finally, astrocytes communicate directly with one another ends of ependymal cells are elongated and extend branching
via gap junctions, forming a very large cellular network for the processes into the adjacent neuropil.
coordinated regulation of their various activities in different
brain regions. Microglia
Less numerous than oligodendrocytes or astrocytes but nearly
› › MEDICAL APPLICATION as common as neurons in some CNS regions, microglia are
small cells with actively mobile processes evenly distributed
Alzheimer disease, a common type of dementia in the
throughout gray and white matter (Figures 9–9a and 9–12).
elderly, affects both neuronal perikarya and synapses within
Unlike other glial cells microglia migrate, with their processes
the cerebrum. Functional defects are due to neurofibrillary
scanning the neuropil and removing damaged or effete syn-
tangles, which are accumulations of tau protein associated
apses or other fibrous components. Microglial cells also con-
with microtubules of the neuronal perikaryon and axon hill-
stitute the major mechanism of immune defense in the CNS,
ock regions, and neuritic plaques, which are dense aggre-
removing any microbial invaders and secreting a number of
gates of β-amyloid protein that form around the outside of
immunoregulatory cytokines. Microglia do not originate from
these neuronal regions.
neural progenitor cells like other glia, but from circulating
blood monocytes, belonging to the same family as macro-
Ependymal Cells phages and other antigen-presenting cells.
Ependymal cells are columnar or cuboidal cells that line the Nuclei of microglial cells can often be recognized in routine
fluid-filled ventricles of the brain and the central canal of the hematoxylin and eosin (H&E) preparations by their small, dense,
spinal cord (Figures 9–9a and 9–11). In some CNS locations, slightly elongated structure, which contrasts with the larger,
the apical ends of ependymal cells have cilia, which facilitate spherical, more lightly stained nuclei of other glial cells. Immu-
the movement of cerebrospinal fluid (CSF), and long micro- nohistochemistry using antibodies against cell surface antigens
villi, which are likely involved in absorption. of immune cells demonstrates microglial processes. When acti-
Ependymal cells are joined apically by apical junctional vated by damage or microorganisms microglia retract their pro-
complexes similar to those of epithelial cells. However, unlike cesses, proliferate, and assume the morphologic characteristics
a true epithelium there is no basal lamina. Instead, the basal and functions of antigen-presenting cells (see Chapter 14).
174 CHAPTER 9 ■ Nerve Tissue & the Nervous System

FIGURE 9–11 Ependymal cells. FIGURE 9–12 Microglial cells.

E V N

E Microglia are monocyte-derived, antigen-presenting cells of the

CNS, less numerous than astrocytes but nearly as common as
neurons and evenly distributed in both gray and white matter.
By immunohistochemistry, here using a monoclonal antibody
against human leukocyte antigens (HLA) of immune-related
cells, the short branching processes of microglia can be seen.
Routine staining demonstrates only the small dark nuclei of the
C
cells. Unlike other glia of the CNS, microglia are not intercon-
nected; they are motile cells, constantly used in immune surveil-
lance of CNS tissues. When activated by products of cell damage
or by invading microorganisms, the cells retract their processes,
begin phagocytosing the damage- or danger-related material,
E and behave as antigen-presenting cells. (X500; Antibody against
HLA-DR and peroxidase)
b (Used with permission from Wolfgang Streit, Department
of Neuroscience, University of Florida College of Medicine,
Gainesville.)

Ependymal cells are epithelial-like cells that form a single layer

lining the fluid-filled ventricles and central canal of the CNS.
(a) Lining the ventricles of the cerebrum, columnar ependymal
cells (E) extend cilia and microvilli from the apical surfaces into
the ventricle (V). These modifications help circulate the CSF and
monitor its contents. Ependymal cells have junctional complexes Schwann Cells
at their apical ends like those of epithelial cells but lack a basal Schwann cells (named for 19th century German histologist
lamina. The cells’ basal ends are tapered, extending processes
Theodor Schwann), sometimes called neurolemmocytes,
that branch and penetrate some distance into the adjacent neu-
ropil (N). Other areas of ependyma are responsible for produc- are found only in the PNS and differentiate from precur-
tion of CSF. (X100; H&E) sors in the neural crest. Schwann cells are the counterparts
(b) Ependymal cells (E) lining the central canal (C) of the spinal to oligodendrocytes of the CNS, having trophic interactions
cord help move CSF in that CNS region. (X200; H&E) with axons and most importantly forming their myelin
sheathes. However unlike an oligodendrocyte, a Schwann
cell forms myelin around a portion of only one axon.
Figure 9–9b shows a series of Schwann cells sheathing the
full length of an axon, a process described more fully with
› › MEDICAL APPLICATION peripheral nerves.
In multiple sclerosis (MS) the myelin sheaths surround-
ing axons are damaged by an autoimmune mechanism Satellite Cells of Ganglia
that interferes with the activity of the affected neurons and
produces various neurologic problems. T lymphocytes and
Also derived from the embryonic neural crest, small satel-
microglia, which phagocytose and degrade myelin debris,
lite cells form a thin, intimate glial layer around each large
play major roles in progression of this disease. In MS, destruc-
neuronal cell body in the ganglia of the PNS (Figures 9–9b
tive actions of these cells exceed the capacity of oligodendro-
and 9–13). Satellite cells exert a trophic or supportive effect
cytes to produce myelin and repair the myelin sheaths.
on these neurons, insulating, nourishing, and regulating their
microenvironments.
 Central Nervous System 175

FIGURE 9–13 Satellite cells around neurons of › CENTRAL NERVOUS SYSTEM

C H A P T E R
ganglia in the PNS.
The major structures comprising the CNS are the cerebrum,
cerebellum, and spinal cord (Figure 9–1). The CNS is com-
pletely covered by connective tissue layers, the meninges, but
S CNS tissue contains very little collagen or similar material,
making it relatively soft and easily damaged by injuries affect-
ing the protective skull or vertebral bones. Most CNS neurons

9
and their functional organization are more appropriately cov-

Nerve Tissue & the Nervous System ■ Central Nervous System

ered in neuroscience rather than histology courses, but certain
N important cells and basic topics will be introduced here.
Many structural features of CNS tissues can be seen in
S unstained, freshly dissected specimens. Many regions show
organized areas of white matter and gray matter, differ-
ences caused by the differential distribution of lipid-rich
myelin. The main components of white matter are myelinated
axons (Figure 9–14), often grouped together as tracts, and the
myelin-producing oligodendrocytes. Astrocytes and microg-
lia are also present, but very few neuronal cell bodies. Gray
L matter contains abundant neuronal cell bodies, dendrites,
astrocytes, and microglial cells, and is where most synapses
S
occur. Gray matter makes up the thick cortex or surface layer
of both the cerebrum and the cerebellum; most white matter is
found in deeper regions. Deep within the brain are localized,
variously shaped darker areas called the cerebral nuclei, each
N containing large numbers of aggregated neuronal cell bodies.
a
In the folded cerebral cortex, neuroscientists recognize
six layers of neurons with different sizes and shapes. The most
conspicuous of these cells are the efferent pyramidal neu-
rons (Figure 9–15). Neurons of the cerebral cortex function
N N in the integration of sensory information and the initiation of
voluntary motor responses.
The sharply folded cerebellar cortex coordinates mus-
cular activity throughout the body and is organized with three
layers (Figure 9–16):

b S S ■ A thick outer molecular layer has much neuropil and

scattered neuronal cell bodies.
■ A thin middle layer consists only of very large neurons
Satellite cells are very closely associated with neuronal cell bod- called Purkinje cells (named for the 19th century Czech
ies in sensory and autonomic ganglia of the PNS and support histologist Jan Purkinje). These are conspicuous even
these cells in various ways. in H&E-stained sections, and their dendrites extend
(a) Nuclei of the many satellite cells (S) surrounding the peri- throughout the molecular layer as a branching basket of
karya of neurons (N) in an autonomic ganglion can be seen by
nerve fibers (Figures 9–16c and d).
light microscopy, but their cytoplasmic extensions are too thin
to see with H&E staining. These long-lived neurons commonly ■ A thick inner granular layer contains various very
accumulate brown lipofuscin (L). (X560; H&E) small, densely packed neurons (including granule cells,
(b) Immunofluorescent staining of satellite cells (S) reveals the with diameters of only 4-5 μm) and little neuropil.
cytoplasmic sheets extending from these cells and surrounding
In cross sections of the spinal cord, the white matter is
the neuronal cell bodies (N). The layer of satellite cells around
each soma is continuous with the myelin sheath around the peripheral and the gray matter forms a deeper, H-shaped mass
axon. Like the effect of Schwann cells on axons, satellite glial (Figure 9–17). The two anterior projections of this gray matter,
cells insulate, nourish, and regulate the microenvironment of the the anterior horns, contain cell bodies of very large motor
neuronal cell bodies. (X600; Rhodamine red-labeled antibody neurons whose axons make up the ventral roots of spinal
against glutamine synthetase) nerves. The two posterior horns contain interneurons which
(Used with permission from Menachem Hanani, Laboratory of
Experimental Surgery, Hadassah University Hospital, Jerusalem,
receive sensory fibers from neurons in the spinal (dorsal root)
Israel.) ganglia. Near the middle of the cord the gray matter surrounds
a small central canal, which develops from the lumen of the
neural tube, is continuous with the ventricles of the brain, is
lined by ependymal cells, and contains CSF.
176 CHAPTER 9 ■ Nerve Tissue & the Nervous System

FIGURE 9–14 White versus gray matter.

A cross section of H&E-stained spinal cord

shows the transition between white matter
G G (left region) and gray matter (right). The gray
matter has many glial cells (G), neuronal cell
A bodies (N), and neuropil; white matter also
A N contains glia (G) but consists mainly of axons
(A) whose myelin sheaths were lost during
preparation, leaving the round empty spaces
shown. Each such space surrounds a dark-
stained spot that is a small section of the
A axon. (X400)
G

FIGURE 9–15 Cerebral cortex.

P
P

A P
P
P A
P
A

a b

(a) Important neurons of the cerebrum are the pyramidal neurons (b) From the apical ends of pyramidal neurons (P), long dendrites
(P), which are arranged vertically and interspersed with numerous extend in the direction of the cortical surface, which can be best
smaller glial cells, mostly astrocytes, in the eosinophilic neuropil. seen in thick silver-stained sections in which only a few other pro-
(X200; H&E) toplasmic astrocytes (A) cells are seen. (X200; Silver)
 Central Nervous System 177

FIGURE 9–16 Cerebellum.

C H A P T E R
ML
ML

9
Nerve Tissue & the Nervous System ■ Central Nervous System
P
GL

GL

a b

ML

P P
P
GL
c d

(a) The cerebellar cortex is convoluted with many distinctive small (c) A single intervening layer contains the very large cell bodies
folds, each supported at its center by tracts of white matter in the of unique Purkinje neurons (P), whose axons pass through the
cerebellar medulla (M). Each fold has distinct molecular layers (ML) granular layer (GL) to join tracts in the medulla and whose multiple
and granular layers (GL). (X6; Cresyl violet) branching dendrites ramify throughout the molecular layer (ML).
(b) Higher magnification shows that the granular layer (GL) Dendrites are not seen well with H&E staining. (X40; H&E)
immediately surrounding the medulla (M) is densely packed with (d) With appropriate silver staining dendrites from each large
several different types of very small rounded neuronal cell bodies. Purkinje cell (P) are shown to have hundreds of small branches,
The outer molecular layer (ML) consists of neuropil with fewer, each covered with hundreds of dendritic spines. Axons from the
much more scattered small neurons. At the interface of these two small neurons of the granular layer are unmyelinated and run
regions a layer of large Purkinje neuron (P) perikarya can be seen. together into the molecular layer where they form synapses with
(X20; H&E) the dendritic spines of Purkinje cells. (X40; Silver)
178 CHAPTER 9 ■ Nerve Tissue & the Nervous System

FIGURE 9–17 Spinal cord.

a b
Lumbar

c d

The spinal cord varies slightly in diameter along its length but in running along the length of the cord. (Center X5, a, b X100; All
cross section always shows bilateral symmetry around the small, silver-stained)
CSF-filled central canal (C). Unlike the cerebrum and cerebellum, (c) With H&E staining the large motor neurons (N) of the ventral
in the spinal cord the gray matter is internal, forming a roughly horns show large nuclei, prominent nucleoli, and cytoplasm
H-shaped structure that consists of two posterior (P) horns rich in Nissl substance, all of which indicate extensive protein
(sensory) and two anterior (A) (motor) horns, all joined by the gray synthesis to maintain the axons of these cells that extend great
commissure around the central canal. distances.
(a) The gray matter contains abundant astrocytes and large neu- (d) In the white commissure ventral to the central canal, tracts
ronal cell bodies, especially those of motor neurons in the ventral (T) run lengthwise along the cord, seen here in cross section
horns. with empty myelin sheaths surrounding axons, as well as small
(b) The white matter surrounds the gray matter and contains tracts running from one side of the cord to the other. (Both
primarily oligodendrocytes and tracts of myelinated axons X200; H&E)
 Central Nervous System 179

Meninges Arachnoid

C H A P T E R
The skull and the vertebral column protect the CNS, but The arachnoid (Gr. arachnoeides, spider web-like) has two
between the bone and nervous tissue are membranes of components: (1) a sheet of connective tissue in contact with
connective tissue called the meninges. Three meningeal the dura mater and (2) a system of loosely arranged trabecu-
layers are distinguished: the dura, arachnoid, and pia maters lae composed of collagen and fibroblasts, continuous with the
(Figures 9–18 and 9–19). underlying pia mater layer. Surrounding these trabeculae is a
large, sponge-like cavity, the subarachnoid space, filled with
Dura Mater CSF. This fluid-filled space helps cushion and protect the CNS

9
The thick external dura mater (L. dura mater, tough mother) from minor trauma. The subarachnoid space communicates

Nerve Tissue & the Nervous System ■ Central Nervous System

consists of dense irregular connective tissue organized as an with the ventricles of the brain where the CSF is produced.
outer periosteal layer continuous with the periosteum of the The connective tissue of the arachnoid is said to be avas-
skull and an inner meningeal layer. These two layers are usually cular because it lacks nutritive capillaries, but larger blood
fused, but along the superior sagittal surface and other specific vessels run through it (Figures 9–18 and 9–19). Because the
areas around the brain they separate to form the blood-filled arachnoid has fewer trabeculae in the spinal cord, it can be more
dural venous sinuses (Figure 9–19). Around the spinal cord clearly distinguished from the pia mater in that area. The arach-
the dura mater is separated from the periosteum of the verte- noid and the pia mater are intimately associated and are often
brae by the epidural space, which contains a plexus of thin- considered a single membrane called the pia-arachnoid.
walled veins and loose connective tissue (Figure 9–18). The In some areas, the arachnoid penetrates the dura mater
dura mater may be separated from the arachnoid by formation and protrudes into blood-filled dural venous sinuses located
of a thin subdural space. there (Figure 9–19). These CSF-filled protrusions, which are

FIGURE 9–18 Spinal cord and meninges.

Posterior median sulcus

D
SD
Anterior median fissure
Pia mater A
Posterior root
SA T
Posterior root ganglion

Spinal nerve BV
Anterior root Subarachnoid space
BV
Arachnoid

P
P
Subdural space

Dura mater

b WM
a Anterior view

(a) A diagram of the spinal cord indicates the relationship of the of the dura from underlying tissue. The middle meningeal layer
three meningeal layers of connective tissue: the innermost pia is the thicker weblike arachnoid mater (A) containing the large
mater, the arachnoid, and the dura mater. Also depicted are the subarachnoid space (SA) and connective tissue trabeculae (T).
blood vessels coursing through the subarachnoid space and the The subarachnoid space is filled with CSF and the arachnoid acts
nerve rootlets that fuse to form the posterior and anterior roots of as a shock-absorbing pad between the CNS and bone. Fairly large
the spinal nerves. The posterior root ganglia contain the cell bod- blood vessels (BV) course through the arachnoid. The innermost
ies of sensory nerve fibers and are located in the intervertebral pia mater (P) is thin and is not clearly separate from the arachnoid;
foramina. together, they are sometimes referred to as the pia-arachnoid or
(b) Section of an area near the anterior median fissure showing the the leptomeninges. The space between the pia and the white mat-
tough dura mater (D). Surrounding the dura, the epidural space ter (WM) of the spinal cord here is an artifact created during dissec-
(not shown) contains cushioning adipose tissue and vascular plex- tion; normally the pia is very closely applied to a layer of astrocytic
uses. The subdural space (SD) is an artifact created by separation processes at the surface of the CNS tissue. (X100; H&E)
180 CHAPTER 9 ■ Nerve Tissue & the Nervous System

FIGURE 9–19 Meninges around the brain.

Superior sagittal sinus

Arachnoid villus

Skin of scalp

Periosteum

Bone of skull

Periosteal layer
Dura mater
Meningeal layer
Subdural space (potential space)
Arachnoid

Subarachnoid space
Arachnoid trabeculae
Pia mater

Cerebral cortex
White matter

The dura, arachnoid, and pia maters also surround the brain and releasing excess CSF into the blood. Blood vessels from the arach-
as shown here the relationships among the cranial meninges are noid branch into smaller arteries and veins that enter brain tissue
similar to those of the spinal cord. The diagram includes arachnoid carrying oxygen and nutrients. These small vessels are initially cov-
villi, which are outpocketings of arachnoid away from the brain, ered with pia mater, but as capillaries they are covered only by the
which penetrate the dura mater and enter blood-filled venous perivascular feet of astrocytes.
sinuses located within that layer. The arachnoid villi function in

covered by the vascular endothelial cells lining the sinuses, are Blood-Brain Barrier
called arachnoid villi and function as sites for absorption of
The blood-brain barrier (BBB) is a functional barrier that
CSF into the blood of the venous sinuses.
allows much tighter control than that in most tissues over
the passage of substances moving from blood into the CNS
Pia Mater tissue. The main structural component of the BBB is the
The innermost pia mater (L. pia mater, tender mother) capillary endothelium, in which the cells are tightly sealed
consists of flattened, mesenchymally derived cells closely together with well-developed occluding junctions, with little
applied to the entire surface of the CNS tissue. The pia does or no transcytosis activity, and surrounded by the basement
not directly contact nerve cells or fibers, being separated from membrane. The limiting layer of perivascular astrocytic
the neural elements by the very thin superficial layer of astro- feet that envelops the basement membrane of capillaries in
cytic processes (the glial limiting membrane, or glia limitans), most CNS regions (Figure 9–10c) contributes to the BBB and
which adheres firmly to the pia mater. Together, the pia mater further regulates passage of molecules and ions from blood
and the layer of astrocytic end feet form a physical barrier to brain.
separating CNS tissue from CSF in the subarachnoid space The BBB protects neurons and glia from bacterial toxins,
(Figure 9–19). infectious agents, and other exogenous substances, and helps
Blood vessels penetrate CNS tissue through long peri- maintain the stable composition and constant balance of ions
vascular spaces covered by pia mater, although the pia in the interstitial fluid required for normal neuronal function.
disappears when the blood vessels branch to form the small The BBB is not present in regions of the hypothalamus where
capillaries. However, these capillaries remain completely covered plasma components are monitored, in the posterior pituitary
by the perivascular layer of astrocytic processes (Figures 9–9a which releases hormones, or in the choroid plexus where CSF
and 9–10c). is produced.
 Central Nervous System 181

Choroid Plexus central canal of the spinal cord, the subarachnoid and perivas-
cular spaces. It provides the ions required for CNS neuronal

C H A P T E R
The choroid plexus consists of highly vascular tissue, elab-
activity and in the arachnoid serves to help absorb mechanical
orately folded and projecting into the large ventricles of the
shocks. Arachnoid villi (Figure 9–19) provide the main path-
brain (Figure 9–20a). It is found in the roofs of the third and
way for absorption of CSF back into the venous circulation.
fourth ventricles and in parts of the two lateral ventricular
There are very few lymphatic vessels in CNS tissue.
walls, all regions in which the ependymal lining directly con-
tacts the pia mater.
Each villus of the choroid plexus contains a thin layer of › › MEDICAL APPLICATION

9
well-vascularized pia mater covered by cuboidal ependymal

Nerve Tissue & the Nervous System ■ Central Nervous System

A decrease in the absorption of CSF or a blockage of outflow
cells (Figure 9–20b). The function of the choroid plexus is from the ventricles during fetal or postnatal development
to remove water from blood and release it as the CSF. CSF is results in the condition known as hydrocephalus (Gr. hydro,
clear, contains Na+, K+, and Cl– ions but very little protein, and water + kephale, head), which promotes a progressive
its only cells are normally very sparse lymphocytes. It is pro- enlargement of the head followed by mental impairment.
duced continuously and it completely fills the ventricles, the

FIGURE 9–20 Choroid plexus.

CSF E
C

CP C

C
V

a b

Ependymal
cells
Capillary
The choroid plexus consists of ependyma and vascularized pia
mater and projects many thin folds from certain walls of the
Pia mater
ventricles.
(a) Section of the bilateral choroid plexus (CP) projecting into
Section of
the fourth ventricle (V) near the cerebellum. (X12; Kluver-Barrera
choroid stain)
plexus (b) At higher magnification each fold of choroid plexus is seen to
be well-vascularized with large capillaries (C) and covered by a
continuous layer of cuboidal ependymal cells (E). (X150)
(c) The choroid plexus is specialized for transport of water and
ions across the capillary endothelium and ependymal layer and
the elaboration of these as CSF.
Cavity of ventricle
CSF forms and
c enters the ventricle
182 CHAPTER 9 ■ Nerve Tissue & the Nervous System

› PERIPHERAL NERVOUS SYSTEM an area termed the mesaxon and a wide, flattened process of
the cell continues to extend itself, moving circumferentially
The main components of the peripheral nervous system (PNS) around the axon many times (Figure 9–21). The multiple lay-
are the nerves, ganglia, and nerve endings. Peripheral ers of Schwann cell membrane unite as a thick myelin sheath.
nerves are bundles of nerve fibers (axons) individually sur- Composed mainly of lipid bilayers and membrane proteins,
rounded by Schwann cells and connective tissue. myelin is a large lipoprotein complex that, like cell membranes, is
partly removed by standard histologic procedures (Figures 9–14
Nerve Fibers and 9–17d). Unlike oligodendrocytes of the CNS, a Schwann
Nerves are analogous to tracts in the CNS, containing axons cell forms myelin around only a portion of one axon.
enclosed within sheaths of glial cells specialized to facilitate With high-magnification TEM, the myelin sheath appears
axonal function. In peripheral nerves, axons are sheathed by as a thick electron-dense axonal covering in which the con-
Schwann cells or neurolemmocytes (Figure 9–9b). The sheath centric membrane layers may be visible (Figure 9–22). The
may or may not form myelin around the axons, depending on prominent electron-dense layers visible ultrastructurally
their diameter. in the sheath, the major dense lines, represent the fused,
protein-rich cytoplasmic surfaces of the Schwann cell mem-
Myelinated Fibers brane. Along the myelin sheath, these surfaces periodically
As axons of large diameter grow in the PNS, they are engulfed separate slightly to allow transient movement of cytoplasm for
along their length by a series of differentiating neurolem- membrane maintenance; at these myelin clefts (or Schmidt-
mocytes and become myelinated nerve fibers. The plasma Lanterman clefts) the major dense lines temporarily disap-
membrane of each covering Schwann cell fuses with itself at pear (Figure 9–23). Faintly seen ultrastructurally in the light

FIGURE 9–21 Myelination of large-diameter PNS axons.

1 Schwann cell becomes

2 The growing process
aligned along the axon Axon completely encloses the
and extends a wide axon but continues its
cytoplasmic process spiral extension.
to encircle it. Schwann cell

Nucleus
Mesaxon

4 The mature Schwann

3 The spiral wrappings cell myelin sheath has
become compacted up to 100 lamellae,
layers of cell with most cytoplasm
membrane (myelin) Cytoplasm of the in the outermost layer
as cytoplasm leaves Schwann cell Myelin sheath
with the cell body.
the growing process.
Compacting
myelin layers

Schwann cell
nucleus

A Schwann cell (neurolemmocyte) engulfs one portion along the wrappings constitute the myelin sheath, with the Schwann cell
length of a large-diameter axon. The Schwann cell membrane body always on its outer surface. The myelin layers are very rich
fuses around the axon and one thin extension of the Schwann cell in lipid, and provide insulation and facilitate formation of action
elongates greatly and wraps itself repeatedly around the axon to potentials along the axolemma.
form multiple, compacted layers. The Schwann cell membrane
 Peripheral Nervous System 183

FIGURE 9–22 Ultrastructure of myelinated and unmyelinated fibers.

C H A P T E R
FM
M

9
Nerve Tissue & the Nervous System ■ Peripheral Nervous System
SC
A
SN

MT NF

M M

A SC

UM

Cross section of PNS fibers in the TEM reveals differences between Unmyelinated axons (UM) are much smaller in diameter, and
myelinated and unmyelinated axons. Large axons (A) are wrapped many such fibers may be engulfed by a single Schwann cell (SC).
in a thick myelin sheath (M) of multiple layers of Schwann cell The glial cell does not form myelin wrappings around such small
membrane. axons but simply encloses them. Whether it forms myelin or not,
The inset shows a portion of myelin at higher magnification in each Schwann cell is surrounded, as shown, by an external lamina
which the major dense lines of individual membrane layers can be containing type IV collagen and laminin like the basal laminae
distinguished, as well as the neurofilaments (NF) and microtubules which underlie epithelia. (X28,000, inset X70,000)
(MT) in the axoplasm (A). At the center of the photo is a Schwann (Used with permission from Dr Mary Bartlett Bunge, The Miami
cell showing its active nucleus (SN) and Golgi-rich cytoplasm (SC). Project to Cure Paralysis, University of Miami Miller School of Medicine,
At the right is an axon around which myelin is still forming (FM). Miami, FL.)
184 CHAPTER 9 ■ Nerve Tissue & the Nervous System

staining layers are the intraperiod lines that represent the

FIGURE 9–23 Myelin maintenance and nodes of
apposed outer bilayers of the Schwann cell membrane.
Ranvier.
Membranes of Schwann cells have a higher proportion of
lipids than do other cell membranes, and the myelin sheath
serves to insulate axons and maintain a constant ionic micro-
environment most suitable for action potentials. Between
adjacent Schwann cells on an axon the myelin sheath shows
small nodes of Ranvier (or nodal gaps, Figures 9–9b,
9–23, and 9–24), where the axon is only partially covered by
interdigitating Schwann cell processes. At these nodes the
axolemma is exposed to ions in the interstitial fluid and has
a much higher concentration of voltage-gated Na+ channels,
which renew the action potential and produce saltatory con-
duction (L. saltare, to jump) of nerve impulses, their rapid
movement from node to node. The length of axon ensheathed
by one Schwann cell, the internodal segment, varies directly
Schmidt- Node of with axonal diameter and ranges from 300 to 1500 μm.
Lanterman clefts Ranvier
Unmyelinated Fibers
Unlike the CNS where many short axons are not myelinated at
all but course among other neuronal and astrocytic processes,
Basal lamina the smallest diameter axons of peripheral nerves are still envel-
oped within simple folds of Schwann cells (Figure 9–25). These
SC SC very small unmyelinated fibers do not however undergo
multiple wrapping to form a myelin sheath (Figure 9–21).
In unmyelinated nerves each Schwann cell can enclose por-
SC tions of many axons with small diameters. Without the thick
myelin sheath, nodes of Ranvier are not seen along unmyelin-
ated nerve fibers. Moreover, these small-diameter axons have
evenly distributed voltage-gated ion channels; their impulse
conduction is not saltatory and is much slower than that of
myelinated axons.

Nerve Organization
In the PNS, nerve fibers are grouped into bundles to form
nerves. Except for very thin nerves containing only unmy-
The middle diagram shows schematically a myelinated periph-
elinated fibers, nerves have a whitish, glistening appearance
eral nerve fiber as seen under the light microscope. The axon
is enveloped by the myelin sheath, which, in addition to mem- because of their myelin and collagen content.
brane, contains some Schwann cell cytoplasm in spaces called Axons and Schwann cells are enclosed within layers of
Schmidt-Lanterman or myelin clefts between the major dense connective tissue (Figures 9–24, 9–26, and 9–27). Imme-
lines of membranes. diately around the external lamina of the Schwann cells is a
The upper diagram shows one set of such clefts ultrastructur-
thin layer called the endoneurium, consisting of reticular
ally. The clefts contain Schwann cell cytoplasm that was not dis-
placed to the cell body during myelin formation. This cytoplasm fibers, scattered fibroblasts, and capillaries. Groups of axons
moves slowly along the myelin sheath, opening temporary with Schwann cells and endoneurium are bundled together as
spaces (the clefts) that allow renewal of some membrane com- fascicles by a sleeve of perineurium, containing flat fibro-
ponents as needed for maintenance of the sheath. cytes with their edges sealed together by tight junctions. From
The lower diagram depicts the ultrastructure of a single
two to six layers of these unique connective tissue cells regu-
node of Ranvier or nodal gap. Interdigitating processes extend-
ing from the outer layers of the Schwann cells (SC) partly cover late diffusion into the fascicle and make up the blood-nerve
and contact the axolemma at the nodal gap. This contact acts barrier which helps maintain the fibers’ microenvironment.
as a partial barrier to the movement of materials in and out of Externally, peripheral nerves have a dense, irregular fibrous
the periaxonal space between the axolemma and the Schwann coat called the epineurium, which extends deeply to fill the
sheath. The basal or external lamina around Schwann cells is
space between fascicles.
continuous over the nodal gap. The axolemma at nodal gaps has
abundant voltage-gated Na+ channels important for impulse Very small nerves consist of one fascicle (Figure 9–28).
conductance in these axons. Small nerves can be found in sections of many organs and
often show a winding disposition in connective tissue.
 Peripheral Nervous System 185

FIGURE 9–24 Node of Ranvier and endoneurium.

C H A P T E R
N
S

9
A longitudinally oriented nerve shows one

Nerve Tissue & the Nervous System ■ Peripheral Nervous System

En node of Ranvier (N) with the axon visible. Col-
lagen of the sparse endoneurium (En), blue in
this trichrome stain, surrounds the Schwann
cells and a capillary (C). At least one Schwann
cell nucleus (S) is also clearly seen. (X400;
Mallory trichome)

Peripheral nerves establish communication between cen- regions and the environment to the CNS. Efferent fibers
ters in the CNS and the sense organs and effectors (muscles, carry impulses from the CNS to effector organs commanded
glands, etc). They generally contain both afferent and efferent by these centers. Nerves possessing only sensory fibers are
fibers. Afferent fibers carry information from internal body called sensory nerves; those composed only of fibers carry-
ing impulses to the effectors are called motor nerves. Most
nerves have both sensory and motor fibers and are called
mixed nerves, usually also with both myelinated and unmy-
FIGURE 9–25 Unmyelinated nerves. elinated axons.

Schwann cell
Unmyelinated axons Ganglia
1 Schwann cell starts
to envelop multiple
Ganglia are typically ovoid structures containing neuronal
axons. cell bodies and their surrounding glial satellite cells sup-
ported by delicate connective tissue and surrounded by a
denser capsule. Because they serve as relay stations to trans-
Axons mit nerve impulses, at least one nerve enters and another
2 The unmyelinated axons
are enveloped by the Schwann cell
exits from each ganglion. The direction of the nerve impulse
Schwann cell, but there are nucleus determines whether the ganglion will be a sensory or an
no myelin sheath wraps autonomic ganglion.
around each axon.

Sensory Ganglia
Sensory ganglia receive afferent impulses that go to the CNS.
Unmyelinated
axon Sensory ganglia are associated with both cranial nerves
Schwann cell (cranial ganglia) and the dorsal roots of the spinal nerves
(spinal ganglia). The large neuronal cell bodies of ganglia
(Figure 9–29) are associated with thin, sheetlike extensions of
During development, portions of several small-diameter axons small glial satellite cells (Figures 9–9b and 9–13). Sensory
are engulfed by one Schwann cell. Subsequently the axons are ganglia are supported by a distinct connective tissue capsule
separated and each typically becomes enclosed within its own and an internal framework continuous with the connective
fold of Schwann cell surface. No myelin is formed by wrapping. tissue layers of the nerves. The neurons of these ganglia are
Small-diameter axons utilize action potentials whose formation
pseudounipolar and relay information from the ganglion’s
and maintenance do not depend on the insulation provided by
the myelin sheath required by large-diameter axons. nerve endings to the gray matter of the spinal cord via syn-
apses with local neurons.
186 CHAPTER 9 ■ Nerve Tissue & the Nervous System

FIGURE 9–26 Peripheral nerve connective tissue: Epi-, peri-, and endoneurium.

Axon
Myelin sheath E N
Endoneurium Fascicle

Perineurium
Epineurium N E
Blood
vessels

Epineurium P
V A

N
b
a

Perineurium Fascicle

Endoneurium

Axon

En
Myelin sheath
S
Blood vessels
c d

(a) The diagram shows the relationship among these three con- (c) As shown here and in the diagram, septa (S) of connective tis-
nective tissue layers in large peripheral nerves. The epineurium (E) sue often extend from the perineurium into larger fascicles. The
consists of a dense superficial region and a looser deep region that endoneurium (En) and lamellar nature of the perineurium (P) are
contains the larger blood vessels. also shown at this magnification, along with some adjacent epi-
(b) The micrograph shows a small vein (V) and artery (A) in the neurium (E). (X200; PT)
deep epineurium (E). Nerve fibers (N) are bundled in fascicles. Each (d) SEM of transverse sections of a large peripheral nerve showing
fascicle is surrounded by the perineurium (P), consisting of a few several fascicles, each surrounded by perineurium and packed with
layers of unusual squamous fibroblastic cells that are all joined at endoneurium around the individual myelin sheaths. Each fascicle
the peripheries by tight junctions. The resulting blood-nerve bar- contains at least one capillary. Endothelial cells of these capillaries
rier helps regulate the microenvironment inside the fascicle. Axons are tightly joined as part of the blood-nerve barrier and regulate
and Schwann cells are in turn surrounded by a thin layer of endo- the kinds of plasma substances released to the endoneurium.
neurium. (X140; H&E) Larger blood vessels course through the deep epineurium that fills
the space around the perineurium and fascicles. (X450)

Autonomic Ganglia Autonomic ganglia are small bulbous dilations in auto-

Autonomic (Gr. autos, self + nomos, law) nerves effect the nomic nerves, usually with multipolar neurons. Some are
activity of smooth muscle, the secretion of some glands, heart located within certain organs, especially in the walls of the
rate, and many other involuntary activities by which the body digestive tract, where they constitute the intramural ganglia.
maintains a constant internal environment (homeostasis). The capsules of these ganglia may be poorly defined among
 Neural Plasticity & Regeneration 187

the sacral portion of the spinal cord. Sympathetic second neu-

FIGURE 9–27 Peripheral nerve ultrastructure.
rons are located in small ganglia along the vertebral column,

C H A P T E R
while second neurons of the parasympathetic series are found
in very small ganglia always located near or within the effector
C organs, for example in the walls of the stomach and intestines.
Parasympathetic ganglia may lack distinct capsules altogether,
F
perikarya and associated satellite cells simply forming a loosely
organized plexus within the surrounding connective tissue.

9
Nerve Tissue & the Nervous System ■ Neural Plasticity & Regeneration
› NEURAL PLASTICITY &
P REGENERATION
En RF Despite its general stability, the nervous system exhibits neu-
SC ronal differentiation and formation of new synapses even in
A adults. Embryonic development of the nervous system pro-
M duces an excess of differentiating neurons, and the cells which
A do not establish correct synapses with other neurons are elimi-
nated by apoptosis. In adult mammals after an injury, the neu-
A A ronal circuits may be reorganized by the growth of neuronal
processes, forming new synapses to replace ones lost by injury.
Thus, new communications are established with some degree
A of functional recovery. This neural plasticity and reforma-
tion of processes are controlled by several growth factors pro-
UM UM duced by both neurons and glial cells in a family of proteins
called neurotrophins.
SC Neuronal stem cells are present in the adult CNS, located
in part among the cells of the ependyma, which can supply new
neurons, astrocytes, and oligodendrocytes. Fully differentiated,
interconnected CNS neurons cannot temporarily disengage
these connections and divide to replace cells lost by injury or
This low-magnification TEM shows a fibroblast (F) surrounded by
collagen (C) in the epineurium (E) and three layers of flattened disease; the potential of neural stem cells to allow tissue regen-
cells in the perineurium (P) that form another part of the blood- eration and functional recovery within the CNS components is
nerve barrier. Inside the perineurium the endoneurium (En) is a subject of intense investigation. Astrocytes do proliferate at
rich in reticulin fibers (RF) that surround all Schwann cells. Nuclei injured sites and these growing cells can interfere with success-
of two Schwann cells (SC) of myelinated axons (A) are visible as ful axonal regeneration in structures such as spinal cord tracts.
well as many unmyelinated axons (UM) within Schwann cells.
(X1200) In the histologically much simpler peripheral nerves,
injured axons have a much greater potential for regeneration
and return of function. If the cell bodies are intact, damaged,
or severed PNS axons can regenerate as shown in the sequence
the local connective tissue. A layer of satellite cells also envel- of diagrams in Figure 9–30. Distal portions of axons, isolated
ops the neurons of autonomic ganglia (Figure 9–29), although from their source of new proteins and organelles, degenerate;
these may also be inconspicuous in intramural ganglia. the surrounding Schwann cells dedifferentiate, shed the myelin
Autonomic nerves use two neuron circuits. The first neu- sheaths, and proliferate within the surrounding layers of con-
ron of the chain, with the preganglionic fiber, is located nective tissue. Cellular debris including shed myelin is removed
in the CNS. Its axon forms a synapse with postganglionic by blood-derived macrophages, which also secrete neuro-
fibers of the second multipolar neuron in the chain located trophins to promote anabolic events of axon regeneration.
in a peripheral ganglion system. The chemical mediator The onset of regeneration is signaled by changes in the
present in the synaptic vesicles of all preganglionic axons is perikaryon that characterize the process of chromatolysis:
acetylcholine. the cell body swells slightly, Nissl substance is initially dimin-
As indicated earlier autonomic nerves make up the auto- ished, and the nucleus migrates to a peripheral position within
nomic nervous system. This has two parts: the sympathetic the perikaryon. The proximal segment of the axon close to the
and the parasympathetic divisions. Neuronal cell bodies of wound degenerates for a short distance, but begins to grow
preganglionic sympathetic nerves are located in the thoracic again distally as new Nissl substance appears and debris is
and lumbar segments of the spinal cord and those of the para- removed. The new Schwann cells align to serve as guides for
sympathetic division are in the medulla and midbrain and in the regrowing axons and produce polypeptide factors which
188 CHAPTER 9 ■ Nerve Tissue & the Nervous System

FIGURE 9–28 Small nerves.

A
S
A S
A F
S
S
C S
A
S
S

A F
a P b

N P
P

N
N
N

c d E

Small nerves can be seen in sections from most organs. which allows nerves to stretch slightly during body movements with
(a) In cross section an isolated, resin-embedded nerve is seen to have no potentially damaging tension on the fibers. (X200; H&E)
a thin perineurium (P), one capillary (C), and many large axons (A) (c) In sections of mesentery and other tissues, a highly wavy or
associated with Schwann cells (S). A few nuclei of fibroblasts can be tortuous disposition of a single small nerve (N) will be seen as mul-
seen in the endoneurium between the myelinated fibers. (X400; PT) tiple oblique or transverse pieces as the nerve enters and leaves
(b) In longitudinal sections the flattened nuclei of endoneurial fibro- the area in the section. (X200; H&E)
blasts (F) and more oval nuclei of Schwann cells (S) can be distin- (d) Often, a section of small nerve will have some fibers cut trans-
guished. Nerve fibers are held rather loosely in the endoneurium and versely and others cut obliquely within the same fascicle, again
in low-magnification longitudinal section are seen to be wavy rather suggesting the relatively unrestrained nature of the fibers within
than straight. This indicates a slackness of fibers within the nerve, the endoneurium (E) and perineurium (P). (X300; H&E)

promote axonal outgrowth. Motor axons reestablish synaptic

connections with muscles and function is restored. fibers grow into columns formerly occupied by motor fibers
connected to motor end plates, the function of the muscle
will not be reestablished. When there is an extensive gap
between the distal and proximal segments of cut or injured
› › MEDICAL APPLICATION peripheral nerves or when the distal segment disappears
Regeneration of peripheral nerves is functionally efficient altogether (as in the case of amputation of a limb), the newly
only when the fibers and the columns of Schwann cells are growing axons may form a swelling, or neuroma, that can be
directed properly. In a mixed nerve, if regenerating sensory the source of spontaneous pain.
 Neural Plasticity & Regeneration 189

FIGURE 9–29 Ganglia.

C H A P T E R
C

9
Nerve Tissue & the Nervous System ■ Neural Plasticity & Regeneration
F
F
F

C F
G

S
N
L

b c

(a) A sensory ganglion (G) has a distinct connective tissue capsule (c) Sympathetic ganglia are smaller than most sensory ganglia
(C) and internal framework continuous with the epineurium and but similar in having large neuronal cell bodies (N), some con-
other components of peripheral nerves, except that no perineu- taining lipofuscin (L). Sheets from satellite cells (S) enclose each
rium is present and that there is no blood-nerve barrier func- neuronal cell body with morphology slightly different from that
tion. Fascicles of nerve fibers (F) enter and leave these ganglia. of sensory ganglia. Autonomic ganglia generally have less well-
(X56; Kluver-Barrera stain) developed connective tissue capsules (C) than sensory ganglia.
(b) Higher magnification shows the small, rounded nuclei of glia (X400; H&E)
cells called satellite cells (S) which produce thin, sheetlike cyto-
plasmic extensions which completely envelop each large neuronal
perikaryon. (X400; H&E)
190 CHAPTER 9 ■ Nerve Tissue & the Nervous System

FIGURE 9–30 Regeneration in peripheral nerves.

a b 2 weeks c 3 weeks d 3 months

In an injured or cut peripheral nerve, proximal axon segments can (c) In the following weeks after injury, muscle fiber shows denerva-
regenerate from their cut ends after a delay. The main changes that tion atrophy, but Schwann cells proliferate to form a compact cord
take place in an injured nerve fiber are shown here. penetrated by the regrowing axon. The axon grows at the rate of
(a) Normal nerve fiber, with its perikaryon, extensive RER (Nissl 0.5-3 mm/d.
substance), and effector cell (muscle). (d) After some months, the nerve fiber regeneration is successful
(b) When the axon is injured, the RER is greatly reduced initially and and functional connections with the muscle fiber are restored.
the nerve fiber distal to the injury degenerates along with its myelin
sheath. Debris is phagocytosed by macrophages (shown in purple).

Nervous System SUMMARY OF KEY POINTS

Development of Nerve Tissue ■ Such nerve communication is transmitted to another neuron or

■ Nervous tissue develops in the early embryo when the dorsal ecto- effector cell via a synapse, where neurotransmitter is released at the
derm neural plate folds lengthwise to form the neural tube, the presynaptic membrane and binds receptors on the postsynaptic
precursor of the CNS, and releases neural crest cells, precursors cell, initiating a new action potential there.
for much of the PNS. Glial Cells
Neurons ■ Glial cells (glia), required to support neurons in many ways, consist
■ There are many kinds of neurons, but all consist of a cell body of six major types:
(perikaryon) containing the nucleus, a long cytoplasmic exten- ■ Oligodendrocytes wrap processes around portions of axons in
sion called the axon, and one or more shorter processes called the CNS, forming myelin sheaths that insulate the axons and
dendrites. facilitate nerve impulses.
■ Neurons use the common cell property of excitability to produce ■ Astrocytes, the most numerous cell of the CNS, all produce hun-
and move an action potential (nerve impulse) along the axon to dreds of processes to cover and provide regulated microenviron-
excite another neuron or other effector cell. ments for neuronal perikarya, synapses, and capillaries.