Neural Plasticity : Part 1.

Plasticity in the Developing

Nervous System: Prenatal Maturation
Beverly Bishop
PHYS THER. 1982; 62:1122-1131.

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NEURAL PLASTICITY
Part 1. Plasticity in the Developing Nervous System
Prenatal Maturation
BEVERLY BISHOP

The origin and development of the nervous system is a gradual process of cell
division, migration, and specialization. The establishment of neural circuits
requires cell-to-cell recognition. Despite an unceasing search, the mechanisms
accounting for this cell-to-cell recognition remain unknown. In contrast, the
stages in prenatal development from conception to birth and the sequence of
events in the formation of the nervous system are known in considerable detail.
The major purpose of Part 1 is to review the ontogeny of the spinal nervous
system, with emphasis on the continuous remodeling phenomena that occur as
a result of changes in neuronal activity or in the biochemical milieu. The
underlying rationale for focusing on the details of prenatal maturation is to
identify and analyze cell-to-cell interactions and to define their critical periods.
This type of information is expected to provide explanations for previously
unexplained developmental phenomena, to improve ability to diagnose and
prognosticate in newborns with congenital anomalies of the nervous system,
and to provide therapists with insights for improving treatment techniques for
neonates with neurological deficits.
Key Words: Nerve growth factors, Nerve tissue, Nervous system, Neuronal plasticity.

The prenatal and postnatal development of the

CNS has always been fascinating to biologists and
therapists, but never more so than in the present
decade. Because interdisciplinary barriers have been
eliminated, scientists from all disciplines have been
combining their efforts in the study of the developing
nervous system. Among the scientists contributing to
this knowledge explosion are the geneticists, embryologists, histochemists, biochemists, physiologists, neuroscientists, pharmacologists, and behavioral scientists. Their results make the scope of the subject
enormous.
The purpose of Part 1 is to emphasize, through
selected examples, some of the important principles
and concepts that have emerged about neuronal plasticity in the developing spinal nervous system.
Dr. Bishop is Professor of Physiology, Department of Physiology,
State University of New York at Buffalo, 120 Sherman Hall, Buffalo,
NY 14214 (USA).

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CELLULAR DIFFERENTIATION
In April 1981, the US Senate held hearings on a
bill to marshal "scientific" evidence as to the moment
when human life begins. Geneticists Leon Rosenberg
forcefully argued that there is "no scientific evidence
which bears on the question of when actual human
life begins."4 He pointed out that a biologist asks the
question differently: rather than asking about when
life starts, he asks about when cellular differentiation
starts. When do cells become irreversibly committed
to their fates? Where, when, and how do neurons
evolve?5, 6 A central question in the analysis of embryonic development is how a collection of cells that
seems to have equal potential for diversifying along
multiple pathways do so in a precisely timed and
patterned sequence to give rise to the complex CNS.7
Biologists discovered nearly a century ago that a
young embryo of the sea urchin, when separated into

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two parts at an early stage, would survive and develop
into two normal embryos. This observation suggested
that at the outset, all cells have equal potential to
develop in a variety of ways. This concept became
dogma until it was shown that the separation of the
egg had to be in a particular plane of the embryo for
two embryos to develop.8 This finding generated important questions concerning mechanisms of cellular
specialization, and the answers awaited discoveries in
molecular biology.
It is now known that cellular determination begins
before fertilization and is mediated through molecular
substances inhomogeneously distributed in the cell's
cytoplasm.8 That is, copies of certain of the mother's
genesmaternal messenger RNAs (mRNAs)exemplify such substances. They function as morphogenetic determinants, become activated after fertilization, and, presumably, alter gene expression. These
substances direct the synthesis of a class of proteins,
called histories, that bind to DNA. Once synthesized,
the histones move to the cell nucleus where sections
of DNA wrap around them to form a structure resembling a string of beads. This process of cell determination starts with the first cell divisions, a time when
there is an enormous burst of histone synthesis. Differentiation of cell types is thought to be selective
suppression of gene activity. Although these discoveries by the molecular biologists are surprising and
exciting, grave difficulties still face the biologist in his
attempts to unravel the developmental secrets of
higher organisms.
ONTOGENY OF THE
SPINAL CORD
After the ova is fertilized, cell division begins. By
the end of one week, there are 100 cells, some of
which already display some specialization. All of the
nervous system evolves from a special sheet of cells,
the neural plate, which is a thickening of the dorsal
ectoderm of the blastula (Fig. 1). Formation of the
neuroectoderm depends on the underlying mesoderm.
If the mesoderm is transplanted to another region of
the embryo, it induces neuralization at the new site.
Presumably, the mesoderm releases some inducing
factor that directs the neuronal specificity. Furthermore, as gastrulation proceeds, the underlying mesoderm exerts its inductive effects in a posterior-anterior
direction so that regions giving rise to the spinal cord
develop earlier than the forebrain. Neural plate cells
are sufficiently specified to have already lost their
ability to become other than neural cells. Cell division
within the neural plate is sufficiently rapid to cause
an upward expansion of the neural plate forming the
neural folds, followed by a progressive invagination,
which forms the neural groove. Ultimately, the neural
folds fuse to form the neural tube, the primordium of
the spinal cord.9"11

Fig. 1. Stages in the formation of the primitive neural

tube.
It appears that communication between cells within
the presumptive neuroectoderm and the underlying
mesoderm is essential for this sequential neuronal
differentiation and axonal growth. If cationic pumps
within cell membranes are poisoned so that membrane potentials are disturbed, neural development is
sorely impaired.
ONTOGENY OF THE DORSAL
ROOT GANGLIA
Some cells migrate from the dorsal margin of the
neural tube to form the neural crest. These cells
undergo further cell division and migrate throughout
the embryo.12 They differentiate into component parts
of the nervous system, including the peripheral
nerves, the entire autonomic nervous system, and the
glial cells. The various cell types are not determined
in the neural crest but instead depend on successive
multicellular interactions, often at their site of migration. Neural crest cells remaining near the neural tube
are the primordia of the dorsal root ganglia (the
sensory cells of the spinal nervous system), and others,
which migrate from the neural crest, become the

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postganglionic ganglia of the autonomic nervous system.

attempted to understand what role it might be playing

in the development of the nervous system. In some
regions of the CNS, cell death is relatively slow and
drawn out over a long period of time. In other regions,
death of an astounding number of cells occurs almost
synchronously, making it an easily recognizable
event. For example, in the mesencephalic nucleus of
the trigeminal complex in the brain stem, the total
number of neurons may be 4,500 at one stage of
development, followed by a dramatic decline to 1,000
in a few days.17 Why 75 percent of the neurons formed
fail to survive is not known. Limited availability of
innervation sites or some other circumstances prevailing in the periphery have been suggested as playing a role.18 If neurons are to survive, they must
establish connections with the right type of target
cells and in the right number. Neurons failing to
make or receive appropriate connections die. The
functional consequence of this naturally occurring
cell death is that it allows for the precise matching of
neurons to their peripheral field of innervation. This
ability adjusts the population size of each group of
neurons appropriately for both the innervation field
to which the neurons send their axons and the receptive field from which they receive afferent input.

TRANSIENT SYNAPSES

SPECIFICATION OF NEUROTRANSMITTER

Recently, appropriate labeling techniques have

made it possible to identify individual afferent fibers
of dorsal ganglia cells and, on the basis of their
peripheral receptor properties, to trace their course
into the CNS where they terminate in unique and
characteristic arbors. In the rhesus monkey, these
sensory fibers enter the dorsal horn of the spinal cord
in the first quarter of the gestational period and form
well-defined synaptic connections with cells in the
superficial border of the dorsal horn.13 These synapses
are only temporary, however, for the entire population of borderline target cells degenerates. The fate of
the axons that terminate on these borderline cells is
not certain. Perhaps some relocate on the later-generated neurons of the substantia gelatinosa; others
may degenerate, as suggested by the large numbers
of bipolar neurons that die during normal development of the dorsal root ganglia.14

A controversial question facing developmental

neurobiologists is to what extent neurotransmitter
specificity is induced by the target cells. The neurons
that make up the adult dorsal root ganglia contain a
wide variety of peptides, including Substance P, enkephalin, serotonin, angiotensin II, somatostatin, vasoactive intestinal peptide, gastrin, and neurotensin
(Fig. 2).19
Cells of the autonomic ganglia, also derived from
neural crest cells, become primarily adrenergic or
cholinergic neurons.20 The specification of transmitter
in autonomic ganglia has been extensively studied in
vivo and in vitro, yet there is no unanimous agreement concerning interpretation of experimental results. It appears likely that the same cell may switch
from adrenergic to cholinergic function under appropriate conditions during development.20-22

HISTOGENIC CELL DEATH

ONTOGENY OF THE FINAL

COMMON PATHWAY

Neuronal cell death during CNS development is

called histogenic cell death and is a poorly understood
phenomenon.15, 16 It is not limited to the dorsal root
ganglia or the dorsal quadrant of the neural tube but
is found in many regions of the nervous system. The
first description of such naturally occurring cell death
in the developing nervous system was published at
the turn of the century, but almost 50 years passed
before other investigators noted the phenomenon and

The somatic motor system is formed by mitosis of

neuroblasts in the ventricular (inner) zone of the
primitive neural tube.23 After dividing, the neuroblasts migrate to the intermediate zone of the neural
tube and group into recognizable cell columns: the
primordia of the brachial and lumbar enlargements
of the spinal cord. Figure 3 shows diagrammatically
that the final positions of motoneurons within a cell

Fig. 2. Peptides contained in cells of the dorsal root

ganglia.

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column correlate with the muscles they will innervate

(eg, neurons to limb muscles lie lateral to those innervating trunk muscles).24, 25 The inductive processes
controlling these cellular migrations and aggregations
remain to be discovered.
Differentiation of a motoneuron. Once a neuron has
migrated to its appropriate cell group, it sends out a
long process, the primordium of the axon. This process lengthens and soon exits from the neural tube. In
migrating to a target cell, the axon establishes a
peripheral pathway in company with developing
blood vessels. The outgrowing process has many terminal branches. The tip of each branch is a special
structure known as a growth cone, which functions
like a "living battering ram blazing a trail to the
target."26 The structural proteins, used to synthesize
the growth cone and to extend the ever-lengthening
axonal process, are synthesized in the cell body of the
neuron and are delivered to the growth cones via an
elaborate axonal transport system.27 If an axon fails
to reach its target, the neuron eventually dies.28, 29
Many more neurons appear in the cell columns of the
ventral horn than surviveanother example of histogenic cell death. It has been shown that 50 percent
or more of the initial set of motoneurons generated in
vertebrate embryos normally die about the time neuromuscular connections begin to form.29
Surviving ventral horn motoneurons undergo considerable differentiation before receiving synaptic inputs from other neurons, and this differentiation continues well into the postnatal period.30 With increasing age, the cell increases in size, the resting membrane potential increases, the action potentials increase in amplitude and decrease in duration,31 and
the after-hyperpolarizations of slow motoneurons become progressively longer. The initial segment of the
axon gradually assumes its very special characteristics
that turn it into the site of action-potential generation.
Before birth, the diameter of the initial segment is
about half that of an adult, whereas its length is the
same.32 As a consequence, the longitudinal resistance
of the initial segment is four-times higher than when
it matures. Another important maturational change
in the initial segment is the dense concentration of
ferric ion-ferrocyanide staining molecules that are
thought to reveal the voltage-dependent sodium channels.33 This high density of sodium channels is
thought to endow the initial segment with a lower
threshold than any other region of the same cell.
CELL-TO-CELL INTERACTIONS

One of the most powerful concepts to emerge from

neurobiology is that of neurotrophism, a host of
phenomena resulting from lifelong interactions between two synaptically joined cells.34-36 The trophic

Fig. 3. The position of a motoneuron within the ventral

horn correlates with the muscle it innervates.

phenomena are essential for the formation and maintenance of neural connections and are involved in the
regulation of structural, metabolic, functional, and
reparative properties of both the presynaptic and
postsynaptic elements. In fact, these cell-to-cell interactions are what endow the nervous system with its
plasticity.
Neuron-target cell interactions. Early in embryonic
development, ventral horn neurons and neural crest
neurons undergo migration and formation of their
peripheral processes before establishing contact with
other cells.9 Yet, cell-to-cell interaction is required for
their complete differentiation. A neural crest sensory
neuron must establish contact with appropriate receptor cells in the periphery before its central process,
directed toward the spinal cord, can establish connections with second-order neurons. The ventral motoneuron must establish contact with the developing
muscle cells in the periphery before dendritic formation is triggered.37 Again, only those neurons that
establish contact with their target cells in the periphery survive and undergo further differentiation. The
motoneuron provides an excellent example of these
cellular interactions. The arrival of a motor axon to
a muscle cell triggers many changes in the neuron
that are thought to be signaled by retrograde axonal
transport.30
Dendritic formation. Once the motoneuron receives
a signal from the periphery that contact with the
target cell is established, dendritic processes begin to
appear.37 First an apical dendrite appears on the soma
opposite the axon, then basal dendrites appear, and
soon the entire cell body is covered with these cellular
extensions that provide an expanded surface area for
synaptic formation. This great dendritic expansion is
as if the neuron were stretching out myriad of fingers

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Fig. 4. Stages in end-piate formation. Upper leftsmall portion of a skeletal muscle cell shown before motor
innervation. Middle leftgrowth cone on a terminal branch of a motor axon arrives at its target, the muscle cell.
Lower leftsynapse formation. Note the absence of extrajunctional acetylcholine receptors but the dense sequestration and synthesis of them at the end-plate. Rightcross-section of mature neuromuscular junction showing
anatomical intimacy of the presynaptic ending, the postsynaptic membrane, and the Schwann cell.

to capture incoming signals from diverse sources.

Dendrites fail to form on those neurons whose outgrowing axons fail to innervate their target cells, and
eventually histogenic cell death occurs. This sequence
of events demonstrates the importance of cellular
interactions for the proper development of the neural
connections.
Bouton formation. Successful arrival of an axon to
the muscle triggers molecular changes that convert
the axon's growth cones to synaptic boutons.38 Organelles of the growth cone are gradually replaced by
synaptic-typical organelles. For example, dense core
vesicles of the growth cone undergo molecular conversion to synaptic vesicles, and mitochondria become dense. After adhesion of the nerve ending to
the muscle cell at specialized sites, the neuron switches
from synthesizing proteins for axonal growth to synthesizing the synaptic transmitter substance acetylcholine.
Enzyme induction. Equally dramatic changes occur
in the muscle cell following arrival of the axon.39 One
of the first events to occur in the neural-triggered
differentiation of the muscle cell is the induction of
1126

acetylcholinesterase synthesis.36, 40 This enzyme rapidly hydrolyzes acetylcholine into acetate and choline
and thereby terminates transmitter action. Innervation of the muscle is essential not only for this enzyme
induction but also for the maintenance of the enzyme's activity throughout life. One of the first events
to follow denervation of a muscle is a rapid decline
and eventual disappearance of acetylcholinesterase
activity.41
End-plate formation. A terminal branch of an axon
terminates on the skeletal muscle cell near the middle
of the fiber, on a site of acetylcholine receptor clusters.42 It has been suggested that this clustering of
acetylcholine receptors on the primitive muscle cells
acts like a target for the outgrowing growth cone.
Once the nerve has made functional contact with the
muscle fiber, the density of acetylcholine receptors
under the nerve terminal rapidly increases as newly
synthesized receptors are inserted into the membrane
(Fig. 4). At the same time, the density of extrajunctional receptors decreases.36 Ultimately, the muscle
membrane lying under the nerve terminal, the motor
end-plate, becomes very specialized structurally and
functionally.35, 36 The motor end-plate undergoes a
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massive infolding that increases the surface area
fivefold or tenfold, permitting a tremendous accumulation of acetylcholine receptors. In fact, end-plate
sensitivity to acetylcholine becomes a thousandfold
greater than that of extrajunctional membrane because of this dense packing of the acetylcholine receptors.43 Unlike extrajunctional membrane, the endplate region is electrically inexcitable.44-46 Its depolarization results from channels opening in response to
acetylcholine or acetylcholine agonists. The integrity
of the end-plate depends on intact innervation. Denervation causes a marked decrease in acetylcholine
receptors at the end-plate zone and an increase in
extrajunctional receptors, making the entire surface
of the muscle cell once again chemically excitable.47, 48
It remains so until innervation is reestablished.
Polyneuronal innervation. When the outgrowing axons originally arrive at the muscle, more than one
may adhere to the muscle and initiate synaptogenesis.
Yet, in the adult mammalian neuromuscular system,
each muscle fiber has one, and only one, end-plate.
Polyneuronal innervation has been documented histologically and physiologically in the immature neuromuscular system,49-51 but the mechanisms underlying the postnatal retraction of the superfluous endings
remain to be elucidated.52, 53
Myelination of peripheral axons. Initially, all outgrowing axon processes are without myelin. It is not
until growth cones arrive at target cells that
"nonneural" Schwann cells start synthesizing the
myelin sheath.54 Because no myelin-stimulating factor
has yet been identified, it is hypothesized that myelinreceptive axons serve as the trigger for myelin formation.55, 56 As shown in Figure 5A and B, one
Schwann cell contributes one segment of the myelin
sheath, which is a multilayered spiral wrapping
around the axon.57 Gaps between these myelin segments are the nodes of Ranvier and are the only sites
where the axonal membrane is exposed to extracellular fluid. The myelin sheath has a high lipid-toprotein ratio, making it an excellent electrical insulator and endowing the internodal segments with high
electrical resistance.
Nodes of Ranvier. Before myelination, the voltagesensitive sodium channels essential for the action
potential are distributed all along the axon.58 The
consequence is that impulse propagation is the slow,
continuous type in which an action potential moves
along the axon like a wave (Fig. 6A). (In mammals,
the conduction velocity might be as low as 1 m/sec.)
With the development of the myelin sheath, the sodium channels become concentrated at the nodes.59 It
is not known whether this remodeling of the nodes is
an increased synthesis of sodium channels at the
nodes, or a redistribution of existing channels, or
both.52 Thus, the internodal segments lose their elec-

Fig. 5A and B. Formation of myelin sheath on a peripheral nerve. A. End view of a cut axon showing how
processes of one Schwann cell envelop the axon. B. With
development, the Schwann cell adds successive spiral
layers of myelin to the axon at any given internode. The
layers become more and more compacted.
trical excitability at the same time the density of
sodium channels is increasing at the nodal regions.
By the time the axon is fully myelinated, local circuit
current in advance of an action potential flows
through the axonal membrane only at the nodes,
where it causes excitation60 (Fig. 6B). Hence, impulse

Fig. 6A and B. A. Continuous conduction before myelination. Note that local circuit current involves the entire
length of the axon. Hence, conduction velocity is very
slow. B. Saltatory conduction in a fully myelinated axon.
Na+ channels cluster at the nodes of Ranvier, and internodes become devoid of Na+ channels. Hence, local
circuit current flows through the membrane only at the
nodes. Since only the nodes undergo the time-consuming
action potential process, conduction velocity is rapid.

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propagation in myelinated axons is the rapid saltatory

type in which the action potential jumps from node
to node54 and conduction velocities assume adult
values. (In the mammal, these may be as high as 50100 m/sec.)

uniquely specified, and modiflability of their connections is lost.

Specification of spinal connections. The development of the spinal cord is characterized by the formation of appropriate synaptic connections among
Changes in conduction velocity. Axonal conduction neurons. These connections are established in a spevelocity increases with time in both cutaneous and cific sequence and provide the neural substrate for
that make their appearance in the premuscle fibers. At least two factors contribute to this the reflexes 64,
65
natal
period.
Spinal reflexes, once established, are
increase. One is the transition from continuous to
66
58, 61
permanent
and
inflexible.
Spinal cord development
saltatory conduction as just described.
The second
characterized by increments in
factor is the increase in fiber diameter with age. This occurs in stages, each 64,
65, 67-69
increase in fiber diameter causes a decrease in the synaptic development.
The differentiation of motoneurons precedes that
internal longitudinal resistance of the axon and an
of
sensory neurons.67, 68 Therefore, the efferent limb
increase in the spatial spread of local circuit current.
Hence, the rate of impulse propagation is increased. of the reflex arc develops before it receives synaptic
During development of the myelin sheath, succes- connections (Fig. 7). However, there is no unanimous
sive layers of myelin are added to the axon (Fig. 5B). agreement as to whether synaptic connections are
At the same time, the axon grows in diameter, causing formed first between motoneurons and interneurons
the myelin membrane to become more and more or between sensory fibers and interneurons. Bodian,
compacted.62 This compaction, added to its high lipid studying the spinal cord of fetal monkeys, found that
content, accounts for myelin's excellent insulating the first central synapses to be formed were those
inputs and small excitproperties. Furthermore, myelin lacks machinery for between the primary64,afferent
65
Subsequently, these inneractive transport and has a very low turnover rate, atory interneurons.
making it one of the body's more stable tissues. vated interneurons made synaptic connections on the
Formation of the myelin sheath in peripheral nerves dendrites of ipsilateral flexor motoneurons. Hence,
is largely complete at birth. Myelination within the the reflex arc subserving the withdrawal or flexion
CNS is far from complete at birth (as will be discussed reflex is among the first spinal reflexes to be established. Consequently, this reflex is primitive, inin Part 2).
grained, and powerful in both prenatal and postnatal
life. Because development of reflex connections proESTABLISHMENT OF NEURAL
ceeds in a rostral-to-caudal direction, arm withdrawal
CIRCUITRY
occurs earlier than leg withdrawal in the fetus.
The central processes of the primary afferent fibers
During CNS development, complex but extraordi- innervating muscle spindles grow into the ventral
narily specific anatomical and functional connections gray to establish synapses directly on those motoneuare established among neurons. Just as the ventral rons innervating the homonymous muscle. The
horn neurons send out axons to make connections monosynaptic reflex can be elicited in kittens even
with the muscles, other immature neurons are sending before birth,30 but it differs from that of the adult cat
out axons to make specific connections with other because maturation of gamma motoneurons occurs
neurons, often in distant parts of the nervous system. after maturation of alpha motoneurons.
How the developing neurites find their way to the
Descending fibers from the higher segments of the
correct synaptic targets is not known. If these neurons cord and brain terminate on interneurons and project
are subjected to abnormal conditions, such as lesions, toward the motoneurons. At about the same time,
viruses, drugs, or altered neural inputs, the patterns inhibitory interneurons in the spinal gray are evolvof their connections may be drastically altered, re- ing. As they mature, their axons make synaptic convealing their high degree of plasticity at this stage of nections on the soma of motoneurons. In addition,
development. These plastic responses to experimental axon collaterals of interneurons begin to grow across
manipulation, however, can be evoked only over a the midline to establish connections in the contralatlimited period. This critical period, during which eral ventral horn. Hence, the neural substrate for
extragenetic factors may alter the development of reciprocal inhibition, crossed extension, and intersegneurons, is unique for each subpopulation of neu- mental reflexes is established early. Connections from
rons.1 The visual system has lent itself very well to descending fibers and interneurons become increasthe study of the critical periods of its various com- ingly more complex. From this complexity emerges
ponents,63 and examples of experiments revealing progressively greater motor capability and increasevidence about them will be described in a later part ingly more versatile patterns of motility.
of this series. Once the critical period for a population
This developmental sequence in the spinal cord has
of neurons has past, these neurons have become served as a model for the development of other CNS

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Fig. 7. Sequential stages (1 through 4) in the formation of spinal neural circuits in the developing spinal cord. The
insets at left show that a sensory neuron of the dorsal root ganglion starts out as a bipolar cell. As it matures, the
peripheral and central processes come closer and closer until the mature primary sensory neuron is a pseudounipolar
cell. (Adapted from Bodian.64)

regions. General features are common to many brain

regions. But developmental biologists remain baffled
about how growing nerve fibers make specific connections with their targets and how neurotransmitter
specificity is induced. Answers to these questions are
expected to elucidate nature's secrets about the induction and termination of developmental plasticity.
This information may suggest methods for extending
or reestablishing plasticity beyond the critical period
as a means for promoting restoration of lost function
caused by congenital abnormalities or birth defects.
SUMMARY
In the fetus, the CNS undergoes continuous remodeling. Initially, these changes are the result of rapid
cell proliferation. In fact, far more cells are generated
than survive. The death of those neurons that fail to
establish appropriate functional connections is called
histogenic cell death. The factors controlling this
natural phenomenon remain to be elucidated. The
growth of an axon appears to be an intrinsic property

of a developing neuron, but the growth and shaping

of dendrites seem dependent on appropriate intercellular interactions. With maturation, peripheral nerve
fibers become ensheathed with myelin and voltagedependent sodium channels mediating electrical excitability cluster at the nodes of Ranvier. An analogous process of segregation occurs at the motor endplate: extrajunctional acetylcholine receptors decrease
and the membrane becomes chemically inexcitable,
while within the neuromuscular junction, receptor
density increases, making the end-plate chemically
excitable. Synapse formation and synapse elimination
among neurons lead to extraordinarily complex
neural networks. Nonetheless, the sequence in which
connections are formed on dendrites and soma of
neurons is not random but orderly and topographical.
By defining the processes by which these developmental phenomena are controlled, the biologist may
be able to understand and possibly compensate for
deficits in the newborn's nervous system resulting
from congenital abnormalities or defects induced at
birth.

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CELLULAR DIFFERENTIATION
4. Point of view: Leon Rosenberg on the "Human Life" bill.
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5. Hamburger V: The life history of a nerve cell. Am Sci 4 5 : 2 6 3 277, 1957
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SUGGESTED READINGS
Reviews under References Cited
Trends in Neuroscience, August 1981

AUDIOVISUAL MEDIA
Illustrated Lectures in Neurophysiology. By B. Bishop
(Available from Audio Visual Medical Marketing, Inc,
404 Park Ave S, New York, NY 10016). Course 706
or Book 6.
Lecture No.
31. Morphogenesis: Origin and Development of Body
Organs
32. Neurogenesis: Origin and Development of the Nervous System
33. Myogenesis: Origin, Differentiation, and Development of Skeletal Muscle
34. Synaptogenesis: Formation of Synapses
35. Development of Nerve Circuits
36. Neurotrophism: Neuron-Target Cell Interactions

Volume 62 / Number 8, August 1982

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1131

Neural Plasticity : Part 1. Plasticity in the Developing

Nervous System: Prenatal Maturation
Beverly Bishop
PHYS THER. 1982; 62:1122-1131.

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