NEURAL PLASTICITY
Part 2. Postnatal Maturation and Function-Induced Plasticity
BEVERLY BISHOP
At birth, the central nervous system has completed most of its early stages of
cell division, migration, and specialization. Much of the neural circuitry has been
laid down. Neuroblasts are continuing to divide only in limited brain regions.
Hence, at birth, most mammals have a nearly full complement of neurons.
Nonetheless, the functional capabilities of the central nervous system of the
newborn have little resemblance to those of the adult. Postnatal maturation
must proceed in the proper sequence and at the proper rate if central nervous
system deficits in the adult are to be avoided. Many of the prenatal maturational
phenomena described in the previous paper continue well into the postnatal
period. The purpose of this paper is to describe some postnatal maturational
mechanisms and to show, by selected examples, the important role that function
and experience play in central nervous system development.
Key Words: Nerve tissue, Nervous system, Neuronal plasticity.
In the case of the afferent fibers from the primary
endings of muscle spindles, the proliferation of the
dorsal root collaterals increases the size of the motoMaturation of motoneurons. Postnatal changes in neuron pool toward which any one afferent fiber
each motoneuron's monospinal motoneurons have been studied in kittens and projects and strengthens
7
synaptic
reflex.
Furthermore,
these dorsal root fibers
found to be correlated with functional and behavioral
no
longer
project
only
toward
homonymous moto1
changes. Following birth, the gray matter of the
neurons,
but
their
expanding
collaterals
project tospinal cord undergoes progressive expansion because
ward
synergistic
motoneurons
as
well.
Thus,
even
of an increase in the cellular volume of the growing
though
the
phasic
monosynaptic
reflex
can
be
elicited
2, 3
neurons. In addition to an increase in the size of
the soma and the length of the axon, the membrane in kittens before birth, it undergoes maturational
of the motoneuron undergoes additional maturational changes after birth. These changes occur in concert
changes. In kittens, the resting membrane potential with maturation of the dorsal root collaterals, their
(RMP) of a motoneuron at birth is about —48 mV, terminals, and their transmitter mechanisms. At the
but when a kitten is two months old, the RMP has same time, the soma and dendrites of the motoneuincreased to about — 60mV, a value maintained rons are increasing in size and their membranes are8
throughout the life of the cell.4 Similarly, the ampli- assuming their adult permeability characteristics.
tude of the action potential increases from —45mV to Tonic stretch reflexes do not 9make their appearance
its adult value of —70mV within two to three months until a kitten is two weeks old. By this time, the small
after birth. These changes in the membrane properties gamma motor axons have established contact with
of the excitable cells are assumed to reflect changes the intrafusal muscle fibers of the muscle spindle.
in the number or function of sodium and potassium Presumably by now, spindle sensitivity has come
under gamma control, completing the neural subchannels within the cell membrane.
strate for the tonic stretch reflexes.
POSTNATAL MATURATION OF
THE SPINAL CORD
Proliferation of dorsal root collaterals. Another sign
of maturation of spinal neurons is the proliferation of
dorsal root collaterals.5, 6 Each collateral forms synapses on second-order neurons, thereby rapidly increasing the number of synaptic boutons on each
target neuron.
1132
Synapse elimination. At birth, several synapses are
found on the initial axonal segment of the cat spinal
motoneuron.10-12 The initial segment is the unmyelinated region of the axon process as it projects from the
soma.13, 14 During the second week of a kitten's life,
the synapses on this region of the motoneuron begin
PHYSICAL THERAPY
PRACTICE
to disappear, and after three weeks, synapses are no
longer seen on this region of the motoneuron.15 In
adult cats, this region of the motoneuron has become
very specialized. It is free of synapses and has developed a high density of voltage-dependent sodium
channels, making it the site of impulse generation.
Studies reveal that the postnatal elimination of synapses on the initial segment occur by the phagocytotic
action of glia cells thought to be immature astrocytes.16'17
Quantitative ultrastructural studies have shown
that synapse elimination is not confined to the initial
segment of the cat spinal motoneuron but includes
synapses on the soma and dendrites as well.16, 17 The
total number of synaptic teminals on the cell body
decreases by about 50 percent during the postnatal
period.17 Synaptic terminals on motoneurons can be
divided into four types based on the shape of their
synaptic vesicles or on their origin: F-type terminals
have flattened vesicles; S-type terminals have spherical vesicles; C-type terminals also have spherical vesicles, but their terminals are large with a pronounced
subsynaptic cistern; and M-type synapses are monosynaptic terminals of dorsal root origin. The Table
shows the postnatal loss of each of these types of
synapses.
The F and S types of synapses are thought to be
removed by a glial phagocytotic process similar to
that occurring at the initial segment. Ultrastructural
evidence seems to indicate however, that C-type synapses are eliminated by a different process. During
the first postnatal week, some C-type terminals appear partially invaginated either in the soma or in the
most proximal parts of the dendrites.18 Presumably,
the motoneuron completely encompasses the terminal, and then lysosomes break down the inclusions.
The phagocytosis appears to include those parts of
the C-terminal associated with synaptic transmission,
including the synaptic vesicles and mitochondria.18
What triggers or controls this interesting and unusual
phagocytotic process is not known, but this process
appears to be part of normal development. The question of whether or not this process takes place under
other circumstances remains to be determined. It
seems strange that a motoneuron can engulf and
devour a particular type of presynaptic bouton terminating on its soma.
Transient synapses. Another remodeling process of
sensory and spinal neurons that is not completed until
well after birth involves synaptic reorganization. In
the rhesus monkey, sensory fibers enter the dorsal
horn during the first quarter of the gestational period
and form well-defined synaptic connections with cells
occupying the most superficial border. Three weeks
later, however, these superficial neurons have degenerated and are replaced by migrating cells that rep-
Volume 62 / Number 8, August 1982
TABLE
Estimated Postsynaptic Loss of Different Types of
Synapses from Alpha Motoneurons17
Type
S
F
C
Total
Loss as No. of Syna p s e s / 1 0 0 sq µm
Loss as % of Synapses Present at
Birth
13.8
13.5
0.2
27.5
55.9
50.0
20.0
52.2
resent the future laminae I and II neurons.19 This loss
of central targets may contribute to the degeneration
of sensory neurons as described in Part 1 under
histogenic cell death.20 Not all sensory neurons deprived of their postsynaptic targets die; some survive
and establish more permanent synapses on the new
superficial dorsal horn neurons.19
Dendritic remodeling. During this period when afferent and efferent connections are being eliminated and
reestablished, the spinal interneurons are also undergoing maturational changes. These include extensive morphological changes in their dendrites. In
newborn mammals, dorsal horn neurons have stubby,
radial dendrites randomly oriented. During the first
two weeks after birth, some dendrites degenerate
while others grow.21 Degenerating dendrites first assume a beaded appearance as vesicles form and then
fuse to create cavities. Dendrites elongate by fusion
of vesicles with existing dendritic membrane.22 The
cues for triggering these morphological changes in
dendritic structure and orientation are unknown.
(Other examples of synapse replacement in adult
vertebrates are given in the recent review by Cotman
et al.23) If the neurobiologist can determine what
controls these dendritic changes, then it may become
possible to use this information to modify or control
dendritic formation in nervous systems with congenitally abnormal dendrites.
Resistance to respecification. Spinal reflex connections are established before birth and, once established, are quite devoid of plasticity. This unexpected
absence of functional plasticity was revealed by experiments performed in the 1940s and 1950s by
Sperry.24-27 He and his colleagues, using reflexes that
coordinate foot movements in the rat, surgically redirected the hindlimb nerves to innervate the antagonistic muscles. The nerves were sectioned and
crossed so that following their regeneration, extensor
motoneurons innervated flexor muscles, and flexor
motoneurons innervated extensor muscles. The result
was reversed limb function. In response to a noxious
stimulus, the foot extended toward the stimulus rather
than withdrawing from it. No amount of training
altered these inappropriate reflex responses. Similar
1133
in the CNS are also satellite cells of neurons, but they
are a different variety of glia cell known as oligodendroglia.30 Any one oligodendroglia cell may send out
its processes to invest 15 to 50 axons as shown in
Figure 1. But each internodal region of any one axon
in the CNS is myelinated by a different oligodendroglialcell.29, 30
With progressive myelination, conduction velocity
in CNS nerve fibers progressively increases, presumably as a result of impulse propagation changing from
continuous to saltatory conduction, analogous to the
changes previously described for prenatal maturation
Fig. 1. One oligodendroglia (the spherical cell) sends out of peripheral nerves.31, 32
extensions of its surface membrane to provide segments
What triggers myelination is not known.29, 33 At the
of myelin sheath for several axons. No two internodal
site
where the outgrowing membrane of an oligodenregions on the same axon are invested by the same
droglial cell makes contact with the axon, there is a
oligodendroglia. (Adapted from Morell and Norton.)29
concentration of glycoprotein.29 It has been suggested
that the glycoprotein plays some role in triggering the
experiments were performed on monkeys, in which
rapid deposition of layers of myelin around the axon.
the nerves to the triceps and biceps muscles were During this period, the oligodendroglial cell is syncrossed. Like the rats, the monkeys failed to correct thesizing several times its own mass of myelin each
these inappropriate reflex responses. Some monkeys day. Hence, nutritional deficiencies in the infant's
did learn to suppress the awkward responses of the diet during this period can cause an insufficiency of
cross-innervated limb, but none learned to perform a myelin formation. This insufficiency may be partially
functionally appropriate response. When sensory compensated for later in life, but in some cases, the
nerves were surgically crossed from one side of the deficit may be permanent.29, 34
body to the other and time was allowed for nerve
Myelin membrane is assembled differently from
regeneration, animals exhibited false reference of sen- membrane of other living cells.35 In most cells, the
sation. For example, in response to a shock to the left protein and lipids are synthesized and assembled into
foot, the right foot was flexed. Again, training was of a vesicle or sac, which then fuses with and becomes
no help.
part of the cell's surface membrane. Subsequently,
The conclusion is that once neural connections other proteins are added primarily to the inner surface
have been laid down in the spinal cord, they resist of the cell membrane. In the case of the oligodenrespecification. Established neural circuits in mam- droglia, newly synthesized myelin is added only near
mals lack intrinsic plasticity. Therefore, when func- the cell body rather than in random patches as occurs
tion is altered as a result of training, the neuronal in other cells.28 The precise way the myelin sheath is
plasticity must be a result of mechanisms other than formed around the CNS axon remains unknown.
respecification of the existing neural connections es- Turnover rates of the lipids and proteins of the myelin
tablished during development.
sheath are also unknown.36 These critical questions
must be answered if the deleterious effects of demyelinating diseases are to be prevented or treated.
Myelination of the CNS. Although myelin formation
Schwann cells in the periphery, when injured by
is largely complete in peripheral nerves at birth, disease or drugs, are capable of proliferating; howmyelination in the brain and spinal cord is not. ever, oligodendroglia responsible for CNS myelinaSubsequent myelination occurs at various times in tion lack the ability to proliferate. Consequently, in
various regions of the CNS and is an important diseases such as multiple sclerosis, demyelination is
process for maturation of the CNS. The proportion essentially irreversible.37 Some evidence suggests that
of white matter of the total cross-sectional area in- surviving oligodendroglia may attempt to remyelinate
creases in all segments of the spinal cord from birth demyelinated regions, but this compensatory response
37
to maturity. In the kitten, this increase is largest is usually too limited to restore function. It has been
2
proposed that central axons, like peripheral axons,
during the first two months after birth.
White matter in the adult brain and spinal cord once demyelinated, fail to conduct, but in time, as
consists of closely packed cylinders of nerve fibers, sodium channels appear along the length of the axons,
gradually revert to continuous slow
most of which are myelinated. Myelin in the CNS is the axons may
38
28
propagation.
Some
investigators have proposed that
different from myelin of peripheral nerves. As deaccount for partial remissions in
scribed in Part 1, the myelin-forming cells in the this mechanism may
37, 39
periphery are Schwann cells.29 Myelin-forming cells multiple sclerosis.
1134
PHYSICAL THERAPY
PRACTICE
FUNCTION-INDUCED
PLASTICITY IN THE BRAIN
Formation of dendritic spines. Maturing neurons in
the cerebral cortex develop small evaginations on
their dendritic surfaces. These lateral extensions of
dendritic neuroplasm are specific postsynaptic receptive structures called dendritic spines (Fig. 2).40 The
dendrites of cortical neurons lack spines in neonatal
rats or kittens, but spines make their appearance
between the 7th and 10th day after birth. Each spine
bears a closely adhering, presynaptic axon terminal.
Usually the spine is convex with its outward curve
fitting against the concave surface of the axon terminal. As a dendritic spine matures, special internal
structures can be seen. These structures are called
spine apparatus and consist of two, three, or more
membrane-bound spaces separated from one another
by dense bands. The spine apparatus is absent in
dendritic spines of animals below mammals on the
phylogenetic scale, suggesting this structure may play
some role in higher brain functions.
Dendritic spines are the last morphological detail
to appear in the development of a nerve cell, and
their appearance signals the functional maturity of a
neuron. When compared with other cell parts, the
dendritic spines display unique plastic properties, and
their growth, at least on cortical pyramidal cells, can
be influenced by the animal's environment. For example, the cortical neurons of rats raised in an enriched environment have a higher density of dendritic
spines than do those of animals raised in a deprived
environment.41, 42 Once developed, spines may degenerate and disappear if their presynaptic input is curtailed, either through disuse or lesion. For example,
neonatal mice raised for 22 to 25 days in darkness, or
after enucleation of one eye, have a significant reduction in the number of dendritic spines on the pyramidal cells of the visual cortex to which the removed
eye would normally project.43'44 Rearing rabbits in
darkness does not produce a change in the number of
dendritic spines, but does cause structural changes in
the spines of neurons in the visual cortex.45 Changes
in appearance of dendritic spines have also, on occasion, been reported in response to chronic alcoholism,
morphine use, chloroform intake, sleep loss, starvation, prolonged exposure to cold, and other physiological stresses. Roentgen ray irradiation produces
progressive changes in and loss of dendritic spines
concomitantly with a gradual emergence of EEG
abnormalities. A marked loss of dendritic spines with
distortion and deformation of the parent dendrites is
often a sequel to those head injuries that result in
epileptic syndromes.
Surgical interruption of presynaptic inputs to dendritic spines causes degeneration of the presynaptic
boutons as would be expected, but subsequent events
Volume 62 / Number 8, August 1982
Fig. 2. Dendritic spines on cortical pyramidal cells from
the brains of a normal 6-month-old infant (left) and a
severely retarded 10-month-old infant (right). Three basic
shapes of spines are seen on the normal dendrite: thin
(TH), mushroom shaped (MS), and stubby (ST). In contrast, spines on the dendrite in the retarded brain are
sparse, long, thin, and entangled. (Reproduced by permission of the author and the publisher.46 Copyright,
1974, by the American Association for the Advancement
of Science.)
at the postsynaptic site are less predictable. At least
three differing effects of presynaptic lesions have been
reported, depending on the brain region lesioned.
One is the complete disappearance of the dendritic
spines along with the degeneration of the presynaptic
boutons. This degeneration suggests that the phagocytic process removes both the presynaptic and postsynaptic elements. In other studies, both the bouton
and dendritic spine appear to be ingested by the
parent dendrite through pinocytotic activity. In the
third and less common situation, the dendritic spines
seem uninvolved in the degenerative process, and
only the presynaptic boutons disappear, with each
vacated synapse on the spines becoming occupied by
a glia cell.
1135
We lack an understanding of the full physiological
significance of dendritic spines. In children with severe mental retardation, dendritic spines are fewer in
number than in normal brains and display abnormal
spine morphology as shown in Figure 2.46 Furthermore, the severity of retardation is closely correlated
with the extent of dendritic spine abnormalities.
Hence, the abnormal spines presumably reflect defective development and lend support to the presently
accepted notion that axo-dendritic synapses on dendritic spines play an as-yet-undefined role in cognitive
and behavioral brain function.
Effects of prolonged repetitive activity. Permanent
alteration in neural activity can occur as a result of
abnormal repetitive activity. A dramatic example of
this can easily be demonstrated in the cat brain. If a
poison, such as strychnine, is applied to a very small
region of the surface of the cortex (eg, to a square
millimeter of the primary auditory area in the temporal lobe), the poisoned cells will soon be spontaneously producing spike activity somewhat similar to
that seen in an EEG during a petit mal seizure.47, 48
This strychnine-induced spike activity is not confined
to the poisoned site but is conducted over neural
circuits to all regions to which the spiking neurons
project. For example, the corresponding area on the
contralateral surface of the cortex displays a similar
spiking pattern. In time, this neurally induced spiking
pattern in the contralateral cortex becomes an inherent property of these cortical neurons as demonstrated
by the persistence of the spiking activity following
extirpation of the cortical tissue in contact with the
poison.
Presumably, in an analogous way, involuntary reiterative activity by a brain-injured patient can, in
time, induce undesirable activity patterns on distant
target neurons. Hence, therapists strive to prevent
unwanted motor postures and patterns in their patients.
Other adaptive changes occur in neural networks
exposed to sustained high-frequency neural activity.
Synapses may swell as a result of high-frequency
activity. Synaptic swelling may enhance neural transmission because of a closer apposition of the presynaptic and postsynaptic membranes.
Some neural networks, particularly in tonic systems, are metabolically equipped to keep pace with a
high-frequency drive. This ability can be demonstrated experimentally by measuring a postsynaptic
response to nerve stimulation before and after a short
period of high-frequency stimulation. Many nerves
will evoke a larger postsynaptic response immediately
after the high-frequency activity than they do before
this activity. This phenomenon is called posttetanic
potentiation (PTP). Careful experimental analysis has
revealed that the presynaptic ending releases more
1136
neurotransmitter per impulse after the high-frequency
stimulation than it does before the stimulation. In
other words, the presynaptic neuron has increased its
synthesis and release of transmitter, thereby keeping
pace with the high-frequency firing. This increase in
transmitter release persists for a short time after cessation of the high-frequency activity. Not all neurons
possess this PTP capability, and so each population
of neurons must be tested. Nonetheless, PTP may be
one important consequence of unwanted, sustained
motor activity. The duration of PTP in most neural
networks is short-lived as shown by the rapid disappearance of PTP once the high-frequency drive is
terminated.
Effects of early experience on sensory development.
Following birth, experience plays a very important
role in the subsequent development of the nervous
system. Furthermore, the role of experience varies
from one brain region to another.
The visual system has been studied in great detail
and found to be extremely dependent on normal
activity for proper development.49 Hubel and Wiesel,
1981 Nobel laureates, performed some of the earliest
and most extensive and refined investigations on the
effects of sensory deprivation on the postnatal development of the visual cortex in cats50-55 and monkeys.56-61 They prevented newborn animals from having normal visual experiences and then correlated
structural deficits with electrophysiological changes
in the visual centers of the CNS.
Prior to Hubel and Wiesel's work, it was assumed
that the visual cortex was laid down as a precisely
arranged structure before the animal was exposed to
any visual experience. But it is now known that at
birth, less than 17 percent of the synapses in the visual
cortex have developed before eye-opening.62, 63 In
fact, normal development of neurons in the visual
system of an adult cat depends on what the cat's
visual experiences were as a kitten between the ages
of three weeks and three months. Vast numbers of
experiments since Hubel and Wiesel's pioneer studies
have led to the currently accepted theory that early
visual experiences determine the synaptic organization of neurons in the visual cortex and correlate with
behavioral deficits.
Figure 3 is a simplified schema showing the visual
pathway from the retina through the lateral geniculate
to the cortex in cat, monkey, and man.64 It shows that
the left retina of each eye projects to the left cortex,
and both right retinas project to the right cortex.
Therefore, each cortical hemisphere receives input
from both eyes. At the lateral geniculate, these bilateral inputs remain anatomically separated; that is,
any one neuron receives input from only one eye, but
at the visual cortex in normal animals, 90 percent of
the cells receive input from both eyes with correPHYSICAL THERAPY
PRACTICE
sponding points on the two retinas projecting to the
same cortical cell.
Over the years, investigators have used ingenious
experimental techniques to control the early visual
experiences of newborn kittens. Examples are intervening to prevent binocular vision65-67 or produce a
convergent squint54, 68 and rearing animals in special
environments to control particular attributes of their
visual experience. These latter experiments include
rearing in the dark,69, 70 with a strobe light to eliminate
movement from the visual experience,71 in an environment with all visual stimuli having a preselected
orientation,72 or some combination of these.73-74 Results from these types of experiments have provided
a tremendous fund of information about the development of the visual system both in normal and
experimental circumstances. The findings have shown
that more or less permanent visual abnormalities
develop if an experimental deprivation is imposed
during a limited but quite specific period during
development. This period, called the critical period, is
species-specific and varies among the multiple attributes of the visual sensation (eg, binocularity, movement detection, acuity, direction detection, orientation sensitivity).75 This new knowledge about critical
periods in the development of the visual system has
important clinical implications. It has prompted earlier treatment of visual abnormalities in the newborn,
thereby preventing permanent visual deficits in many
cases.76
Effects of monocular deprivation. One experimental
approach that has been commonly used is to suture
the lid of one eye of a newborn kitten shut so the
animal sees with only one eye for the first three
months of life.50-52, 77 Monocular deprivation leads to
gross functional abnormalities. In the visual cortex of
a normal animal, 90 percent of the cortical cells
respond to input from either eye, but in an animal
with a sutured lid, essentially all neurons of the visual
cortex respond only to stimulation of the unsutured
eye. In other words, three months of monocular deprivation early in the kitten's life render the sutured
eye incapable of driving cortical visual cells. In these
monocularly deprived animals, the cells in the retina
and lateral geniculate bodies appear to respond quite
normally, suggesting that the visual cortex is the
major site of the functional deficit. Although neither
the retina nor the cortex shows gross anatomical
changes, the lateral geniculate has smaller cells and
is thinner than normal, as if it had an arrested growth
or had undergone atrophy. The visual neurons develop more normally if the sutured eye is exposed to
as little as one hour of light up to the age of four
weeks. Monocular deprivation during the first three
months of life produces behavioral deficits as well.
The animals develop a severe and irreversible moVolume 62 / Number 8, August 1982
Fig. 3. A diagram of the visual pathway from the retina
through the lateral geniculate to the cortex in cat, monkey, and man. Note that fibers from both nasal retinas
cross the optic chiasm and thereby project to the contralateral cortex; fibers from the temporal retinas project
unilaterally to their ipsilateral cortex. Therefore, a visual
stimulus presented only in the left visual field of the right
eye will excite cells in the right visual cortex.
nocular dominance. For all practical purposes, the
eye that was sutured shut during the critical period is
functionally blind. Some recovery from the effects of
monocular deprivation occurs if the animal is forced
to use the deprived eye.78"83
Effects of early selective exposure. In other experimental paradigms, kittens have been reared in a
special environment where they see only one orientation of visual stimuli. The neurophysiological results
of this rearing are shown in Figure 4. As discussed
previously, in normally reared cats, 90 percent of the
total cells in the visual cortex are binocular units in
that they can be excited by input from either eye. The
bar graphs in Figure 4 indicate the number of units
that are preferentially stimulated by lines of a specific
orientation with respect to the horizontal plane. Note
that in normally reared animals, about equal numbers
of cells respond to each orientation of the stimulus.
The other graphs of Figure 4 show the results from
animals selectively reared in environments in which
they saw only lines oriented as indicated in the insets.
In the selectively reared cats, the units are monocular.
In animals permitted to see only horizontal lines, the
visual neurons respond only to horizontal stimuli,
1137
whose neurons detected only vertical lines. The behavioral result was a cat who could maneuver around
the vertical legs of furniture but never attempted to
jump onto the horizontal seat of a chair or onto a
tabletop. Animals reared in an environment of horizontal stripes never jumped onto a table or chair seat
but would bump into the vertical legs of the same
furniture as if blind to them.
These remarkable behavioral changes, imposed by
the unusual sensory experience, were permanent and
resulted from the permanent alterations in the synaptic organization of the visual cortex. Furthermore,
for these visual abnormalities to occur, the sensory
deprivation had to be imposed during a limited but
specific period in development—the critical period.
Effects of binocular deprivation. Deficits in binocular
depth perception can be created experimentally in
cats by preventing them as young kittens from seeing
with both eyes at the same time.65, 67 If an opaque lens
is placed alternately over one eye, then the other, the
number of cortical cells that can be activated through
both eyes is greatly reduced. Cats reared without
binocular input suffer lifelong deficits in stereoscopic
depth perception while retaining normal acuity in the
two eyes. From these results, it is concluded that
binocular neurons become binocular during a critical
period, and if binocular neurons are not formed
during the critical period, a permanent deficit in
binocular depth perception persists.
In summary, it is now well-established that many
of the functional connections of single cells in the
Fig. 4. Effects of early selective exposure. Number of visual cortex of newborn kittens are susceptible to
neurons with preferred orientation within each of four disruption by abnormal visual experiences during the
ranges. The shaded areas in each histogram indicate the first few months of life.74 Monocular deprivation
orientation of the lines (± 22.5%) to which the animals
were exposed during their first four months of life. The causes functional blindness in the deprived eye and
lines inscribed in each circle illustrate the patterns pre- disturbed depth perception. Binocular deprivation
sented during rearing. Upper: A full range of orientationcauses disturbed stereoscopic depth perception. Expreferences was found in animals raised in a normal posure to visual stimuli of selected orientation results
visual environment. Lower: 1) In animals that viewed onlyin abnormal frequency distributions of orientationhorizontal and vertical lines, most orientation-sensitive
neurons responded preferentially to horizontal or to ver- sensitive neurons. The development of functional abtical stimuli. 2) In animals that viewed only diagonal lines,normalities and the development of normal visual
most orientation-sensitive neurons responded preferen- function require appropriate use of both eyes
tially to horizontal or to vertical lines. The rest were throughout critical periods.
activated most strongly by lines with an orientation matching that of the patterns presented during rearing. (Repro- Do these findings have any relevance for humans?
duced by permission of the author and the publisher.72 Children with strabismus (cross-eyes) or astigmatism
Copyright, 1975, by the American Association for the (blurred focus in a specific direction) must have this
Advancement of Science.)
abnormal function corrected before or during the
critical period if the visual system is to develop normally.76 Although precise information about the rate
with essentially no cells responding to oblique or
of development of human visual deficits is lacking,
the data about cats and monkeys serve as model
vertical stimuli. In other words, units responding to
the experienced orientation predominate, and units systems. Ultimately, precise information about the
critical periods of man's visual system may become
tuned to orthogonal orientations that were absent in
available.
their visual environment are absent. A kitten reared
The work on the effects of deprivation on the
in the environment of only vertical lines (Fig. 4—
structure and function of the visual cortex demonright eye) matured into a cat with a visual cortex
1138
PHYSICAL THERAPY
PRACTICE
strates the importance of early experience for proper
development of the visual system. In an analogous
manner, early auditory deprivation (ie, monaural
deprivation of sound) has been shown to greatly
disturb binaural interaction at the level of the inferior
colliculus.84 These identified abnormalities in binaural interaction were found to have a critical period
between 10 and 60 days after birth in rats.85 It seems
highly likely that many, if not all, sensory systems of
the brain are shaped by early experience. Stimulation
has long been recognized as a requirement for growth
and function in behavioral development.86
Effects of experience on motor development. Differentiation of the contractile properties of fast-twitch
and slow-twitch muscle is a gradual process that
continues well into the postnatal period and has been
extensively studied in the limb muscles of newborn
kittens.87, 88 At birth, all limb muscles in the kitten
have similar slow-twitch times of about 80 msec;
however, in the adult animal, the fast muscles (eg,
gastrocnemius) have a twitch time three-times shorter
than that of the slow muscles (eg, soleus).87 This
differentiation occurs over the first 16 weeks of postnatal life, as shown in the upper graph of Figure 5.
The difference in speed of contraction between the
fast and slow muscle is apparent within a few days
after birth. By the end of the first month, the fast
muscle has attained a contraction time that remains
virtually unaltered thereafter. The slow muscle initially shows an increased speed of contraction but
eventually undergoes a slowing process requiring
about 12 weeks to complete.
Effects of disuse. The difference in the time course of
differentiation of the speeds of contraction for fast
and slow muscles led investigators to question the
nature of the controlling influence. To determine
whether the controlling influence was inherent in the
muscle or was the result of some neurotrophic influence, the following experiments were performed.
The spinal cords of one group of newborn kittens
were transected between L1 and L2 to isolate the
motoneurons innervating the limb muscles from descending excitatory influences.87, 89 In another group
of animals, not only were the spinal cords transected,
but also the lumbar dorsal roots were cut bilaterally
as a means of isolating the lumbar motoneurons from
incoming as well as descending signals. These experimental procedures produced disuse atrophy, as
would be expected, but no denervation effects. In
animals with the functionally isolated lumbar motoneurons, differentiation of slow muscles failed to
occur. At the end of 14 weeks, both muscles had
equally fast contraction times, with the fast muscles
being little different from those in intact animals, as
Volume 62 / Number 8, August
1982
Fig. 5. Upper: Time course of development of adult
speed of contraction in A) slow (soleus and crureus) and
B) fast (flexor digitorum longus, flexor hallucis longus and
medial gastrocnemius) muscles of kittens (solid lines).
Lower: Postulated curves for the same muscles in the
absence of neural influences (as a result of spinal transection and dorsal rhizotomy) are shown by the dashed
curves. The crosshatched areas reflect the contribution
of neural influences. (Adapted from Buller et al.87)
shown in the lower graph of Figure 5. Speeding up of
contraction time in fast muscle occurred whether or
not the fast motoneurons were active, suggesting that
their progressive decrease in contraction time was a
genetically determined property inherent in fast muscle independent of neurotrophic influences. In contrast, in the absence of neural activity, slow muscles
failed to slow, suggesting that the slowing process
must be dependent upon influences exerted either by
motoneuron activity, or muscle activity, or by both.
These experiments of the 1960s sparked interest
and controversy regarding the mechanisms of muscle
differentiation. Despite two decades of intensive investigation, it is still not known whether the differentiation of slow muscle is due to neurotrophic regulation by the motoneuron or to muscle activity per
se. There is experimental evidence supporting both
mechanisms as described below.
Effects of cross-reinnervation. A useful experimental
approach for studying the neurotrophic action of
nerve on skeletal muscle is the cross-reinnervation
technique: the nerve from a fast muscle (eg, flexor
digitorum longus) is cut and redirected to reinnervate
a slow muscle (eg, soleus), and the nerve from the
slow muscle is cut and redirected to reinnervate a fast
1139
muscle. In cats, this cross-reinnervation causes the
twitch time of the fast muscle to become indistinguishable from that of the slow muscle and that of
the slow muscle to change in the direction of the fast
muscle, but the transformation is not complete.89
These experimental observations not only have been
confirmed repeatedly90, 91 but have been extended to
show that a motoneuron regulates many aspects of
gene expression in the muscle it innervates.92, 93 In
addition to changing a muscle's contractile speed,
cross-reinnervation induces changes in the profile of
the muscle's metabolic enzymes,94-96 the structure of
its myosin molecules,97, 98 the distribution of acetylcholine receptors along its length,99 and the properties of the sarcoplasmic reticulum100 and sarcolemma.101, 102
These experimental results made it all the more
imperative to determine the mechanisms by which a
motor nerve exerts regulation over the physiological,
morphological, and biochemical characteristics of the
muscle it innervates.
Effects of disrupting axoplasmic flow. Local application of colchicine to a motor nerve, by disrupting
microtubules, blocks axoplasmic flow103, 104 without
interfering with the propagation of nerve impulses or
the release of neural transmitter.105, 106 Yet the muscles
innervated by colchicine-treated axons develop many,
but not all, signs of denervation.105, 106 The muscle
membrane becomes chemosensitive, develops tetrodotoxin-resistant action potentials, and becomes partially depolarized with no appearance of fibrillation
potentials nor increase in input resistance of the muscle membrane. 107 These results suggest that colchicine,
by blocking axonal transport, deprives the muscle of
some "trophic" substance ordinarily delivered by the
nerve.107, 108 Not everyone accepts this interpretation,
however, because an unanswered question is whether
or not colchicine may have a direct effect on muscle
as well as on axoplasmic flow.109
Effects of muscle activity. Experimental evidence suggesting that the pattern of muscle activity may control
the contractile properties of muscle is shown in Figure
6.110 In the experiments giving rise to these results, a
fast muscle—the extensor digitorum longus—in rabbits was continuously stimulated for 20 weeks with
repetitive electric shocks delivered to the motor nerve
through chronically implanted electrodes.
Comparison of records B and C of Figure 6 shows
that the twitch of the fast muscle is dramatically
slowed at the end of 20 weeks of stimulation. A
comparison of A and C of Figure 6 shows that, in
fact, the stimulated fast muscle (C) contracts as slowly
as the slow soleus (A), if not more slowly. In addition,
the stimulated fast muscle (C) has increased its resistance to fatigue and has altered its myosin molecules.
These results suggest that the pattern of activity imposed by the motor nerve upon a muscle may determine the muscle's time course of contraction. Similar
results have been reported for cat fast muscle (flexor
digitorum longus).111 Subsequent experiments have
shown that long-term, low-frequency stimulation of
rabbit fast-twitch muscle induces the production of
myosin light chains characteristic of slow muscle.112
Despite these interesting observations, it remains
controversial whether the altered mechanical responses of the chronically stimulated muscle are the
direct result of the pattern of activity, the indirect
Fig. 6. Effects of prolonged electrical stimulation on iso- consequence of an alteration in axonal transport (and,
metric twitch of rabbit extensor digitorum longus (EDL) hence, in the delivery of some as-yet-unknown neumuscle. Records A, B, and C are isometric twitch con- rotrophic substance), or both.
tractions from the normal, slow soleus muscle, from the
Whatever the mechanism, the fact remains that the
fast EDL muscle of the right, nonstimulated limb, and fromcontractile properties of skeletal muscle are altered as
the left EDL muscle, which had been stimulated continuously for 20 weeks, respectively. (Adapted from Salmons a result of the activity pattern. Have therapists ever
asked the questions, What changes are occurring in
and Vrbova.110)
1140
PHYSICAL THERAPY
PRACTICE
a spastic muscle as a result of its prolonged, uncon­
trolled activity? and Do these changes further com­
pound the patient's motor problems?
In summary, the maturation of skeletal muscle
depends not only on the muscle's inherent properties
but also on the effects imposed by its motor nerve.
Slow-twitch muscle must be used in the early post­
natal period if it is to acquire its adult slow contractile
properties. In contrast, fast-twitch muscle assumes its
adult speed of contraction whether it is active or not
in the early postnatal period. This independent dif­
ferentiation, however, can be overridden by pro­
longed stimulation of its motor nerve with low-fre­
quency shocks.
CONCLUSION
Environmental influences during certain periods of
early postnatal life have an effect on later develop­
ment and behavior. Defining the mechanisms
whereby early experience induces such long-lasting,
and perhaps permanent, effects upon the behavior of
the organism is a challenge for today's neuroscientists.
Furthermore, such information is bound to have an
impact on future treatment procedures.
Editor's note: Self-assessment quizzes, written by
the author, on Parts 1 and 2 are published in this
issue.
REFERENCES
POSTNATAL MATURATION OF THE SPINAL CORD
Maturation of Motoneurons
1. Huizar P, Kuno M, Miyata Y: Differentiation of motoneurones and skeletal muscles in kittens. J Physiol (Lond)
252:465-479, 1975
2. Sato M, Mizuno N, Konishi A: Postnatal differentiation of
cell body volumes of spinal motoneurons innervating slowtwitch and fast-twitch muscles. J Comp Neurol 175:27-36,
1977
3. Cullheim S, Ulfhake B: Relations between cell body size,
axon diameter and axon conduction velocity of triceps
surae alpha motoneurons during postnatal development in
the cat. J Comp Neurol 188:679-685, 1979
4. Kellerth J-O, Melstrom A, Skoglund S: Postnatal excitability
changes of kitten motoneurones. Acta Physiol Scand
8 3 : 3 1 - 4 1 , 1971
Proliferation of Dorsal Root Collaterals
5. Skoglund S: Central connections and functions of muscle
nerves in the kitten. Acta Physiol Scand 50:222-237, 1960
6. Skoglund S, Romero C: Postnatal growth of spinal nerves
and roots: A morphological study in the cat with physiolog­
ical correlations. Acta Physiol Scand [Suppl] 260:1-50,
1965
7. Skoglund S: Muscle afferents and motor control in the
kitten. In Granit R(ed): Muscular Afferents and Motor Con­
trol. Stockholm, Sweden Nobel Symposium 1, 1966, pp
245-259
8. Mellstrom A, Skoglund S: Quantitative morphological
changes in some spinal cord segments during postnatal
development. Acta Physiol Scand [Suppl] 331:1-84, 1969
9. Skoglund S: On the postnatal development of postural
mechanisms as revealed by electromyography and myog­
raphy in decerebrate kitten. Acta Physiol Scand 4 9 : 2 9 9 317, 1960
Synapse Elimination
10. Conradi S, Skoglund S: Observations on the ultra-structure
and distribution of neuronal and glial elements on the mo­
toneuron surface in the lumbosacral spinal cord of the cat
during postnatal development. Acta Physiol Scand [Suppl]
333:5-52, 1969
11. Conradi S, Skoglund S: Observations on the ultra-structure
of the initial motor axon segment and dorsal root boutons
on the motoneurons in the lumbosacral spinal cord of the
cat during postnatal development. Acta Physiol Scand
[Suppl] 333:53-76, 1969
12. Conradi S, Ronnevi LO: Ultrastructure and synaptology of
the initial axon segment of cat spinal motoneurons during
early postnatal development. J Neurocytol 6:195-210,
1977
13. Palay SL, Sotelo C, Peters A, et al: The axon hillock and
the initial segment. J Cell Biol 3 8 : 1 9 3 - 2 0 1 , 1968
Volume 62 / Number 8, August 1982
14. Conradi S: Observations on the ultrastructure of the axon
hillock and initial axon segment of lumbosacral motoneu­
rons in the cat. Acta Physiol Scand [Suppl] 332:65-84,
1969
15. Purvis D, Lichtman JW: Elimination of synapses in the
developing nervous system. Science 210:153-157, 1980
16. Ronnevi LO, Conradi S: Ultrastructural evidence for spon­
taneous elimination of synaptic terminals on spinal moto­
neurons in the kitten. Brain Res 80:335-339, 1974
17. Conradi S, Ronnevi LO: Spontaneous elimination of syn­
apses on cat spinal motoneurons after birth: Do half of the
synapses on cell bodies disappear? Brain Res 9 2 : 5 0 5 510, 1975
18. Ronnevi LO: Spontaneous phagocytosis of C-type synaptic
terminals by spinal α-motoneurons in newborn kittens: An
electron microscopic study. Brain Res 1 6 2 : 1 8 9 - 1 9 9 , 1 9 7 9
Transient Synapses
19. Knyihar E, Csillik B, Rakic P: Transient synapses in the
embryonic primate spinal cord. Science 202:1206-1209,
1978
20. Jessell TM, Yamamoto M: Development of spinal sensory
systems. Nature 2 8 8 : 6 4 0 - 6 4 1 , 1980
Dendritic R e m o d e l i n g
2 1 . Gobel SJ: Golgi studies of the neurons in Layer 1 of the
dorsal horn of the medulla (trigeminal nucleus caudalis). J
Comp Neurol 180:375-394, 1978
22. Falls W, Gobels SF: Golgi and EM studies of the formation
of dendritic and axonal arbors: The interneurons of the
substantia gelatinosa of Rolando in newborn kittens. J
Comp Neurol 187:1-18, 1979
23. Cotman CW, Nieto-Sampedro M, Harris EW: Synapse re­
placement in the nervous system of adult vertebrates. Phys­
iol Rev 61:684-784, 1981
Resistance to Respecification
24. Sperry RW: Transplantation of motor nerves and muscles
in the forelimb of the rat. J Comp Neurol 7 6 : 2 8 3 - 3 2 1 , 1942
25. Sperry RW: The problem of central nervous system reor­
ganization after nerve regeneration and muscle transposi­
tion. Quarterly Review of Biology 20:311 - 3 6 9 , 1945
26. Sperry RW: Effect of crossing nerves to antagonistic limb
muscles in the monkey. Archives of Neurology and Psy­
chiatry 58:452-473, 1947
27. Sperry RW: The growth of nerve circuits. Sci Am
201(5):68-75, 1959
Myelination of the CNS
28. Caley DW, Butler AB: Formation of central and peripheral
myelin sheaths in the rat: An electron microscopic study.
Am J Anat 140:339-348, 1974
1141
29. Morell P, Norton WT: Myelin. Sci AM 242(5):88-116, 1980
30. Bunge RP: Glial cells and the central myelin sheath. Physiol
Rev 4 8 : 1 9 7 - 2 5 1 , 1968
3 1 . Bostock H, Sears TA: The internodal axonal membrane:
Electrical excitability and continuous conduction in segmental demyelination. J Physiol (Lond) 2 8 0 : 2 7 3 - 3 0 1 , 1 9 7 8
32. Chiu SY, Ritchie JM: Potassium channels in nodal and
internodal axonal membrane of mammalian myelinated fibers. Nature 2 8 4 : 1 7 0 - 1 7 1 , 1980
3 3 . Weinberg HJ, Spencer PS: Studies on the control of myelinogenesis: 2. Evidence of neuronal regulation of myelin
production. Brain Res 1 1 3 : 3 6 3 - 3 7 8 , 1976
34. Gozzo S, D'Udine B: Diet deprived in essential fatty acids
affects brain myelination. Neuroscience Letters 7:267-276,
1978
35. Franks NP: Myelin structure. Nature 259:447, 1976
36. Davison AN, Peters A: Myelination. Springfield, IL, Charles
C Thomas, Publisher, 1970
37. Prineas J: Pathology of the early lesion in multiple sclerosis.
Hum Pathol 6:531-554, 1975
38. Kocsis JD, Waxman SG: Absence of potassium conductance in central myelinated axons. Nature 2 8 7 : 3 4 8 - 3 4 9 ,
1980
39. Smith KJ, Blakemore WF, McDonald WI: Central remyelination restores secure conduction. Nature 280:395-396,
1979
FUNCTION-INDUCED PLASTICITY IN THE BRAIN
Formation of Dendritic S p i n e s
40. Scheibel ME, Scheibel AB: On the nature of dendritic
spines: Report of a workshop. Communications in Behavioral Biology 1(4) Part A:231-265, 1968
4 1 . Schapiro S, Vukovich KR: Early experience effects upon
cortical dendrites: A proposed model for development. Science 167:292-294, 1970
42. Globus A, Rosengweig MR, Bennett EL, et al: Effects of
differential experience on dendritic spine counts in rat
cerebral cortex. J Comp Physiol Psychol 8 2 : 1 7 5 - 1 8 1 ,
1973
4 3 . Valverde F: Apical dendritic spines of the visual cortex and
light deprivation in the mouse. Exp Brain Res 3:337-352,
1967
44. Valverde F: Structural changes in the area striata of the
mouse after enucleation. Brain Res 5:274-292, 1968
4 5 . Globus A, Scheibel AB: The effect of visual deprivation on
cortical neurons: A Golgi study. Exp Neurol 1 9 : 3 3 1 - 3 4 5 ,
1967
46. Purpura D: Dendritic spine "Dysgenesis" and mental retardation. Science 1 8 6 : 1 1 2 6 - 1 1 2 8 , 1974
Effects of Prolonged Repetitive Activity
47. Gastaut H, Fischer-Williams M: The physiopathology of
epileptic seizures. In Field J, Magoun HW, Hall VE(eds):
Handbook of Physiology: Neurophysiology. Washington,
DC, American Physiological Society, 1959, vol 1, pp 3 4 0 352
48. Towe AL, Mann MD: Effect of strychnine on the primary
evoked response and on the corticofugal reflex discharge.
Exp Neurol 3 9 : 3 9 5 - 4 1 3 , 1973
EFFECTS OF EARLY EXPERIENCE ON SENSORY
DEVELOPMENT
49. Hubel DH: The visual cortex of normal and deprived monkeys. Am Sci 6 7 : 5 3 2 - 5 4 3 , 1979
50. Hubel DH, Wiesel TN: Receptive fields, binocular interaction
and functional architecture in the cat's visual cortex. J
Physiol (Lond) 160:106-154, 1962
5 1 . Hubel DH, Wiesel TN: Receptive fields of cells in striate
cortex of very young, visually inexperienced kittens. J Neurophysiol 2 6 : 9 9 4 - 1 0 0 2 , 1963
52. Wiesel TN, Hubel DH: Single-cell responses in striate cortex
of kittens deprived of vision in one eye. J Neurophysiol
2 6 : 1 0 0 3 - 1 0 1 7 , 1963
1142
53. Wiesel TN, Hubel DH: Comparison of the effects of unilateral
and bilateral eye closure on cortical unit responses in
kittens. J Neurophysiol 2 8 : 1 0 2 9 - 1 0 4 0 , 1965
54. Hubel DH, Wiesel TN: Binocular interaction of striate cortex
of kittens reared with artificial squint. J Neurophysiol
2 8 : 1 0 4 1 - 1 0 5 9 , 1965
55. Hubel DH, Wiesel TN: The period of susceptibility to the
physiological effects of unilateral eye closure in kittens. J
Physiol (Lond) 2 0 6 : 4 1 9 - 4 3 6 , 1970
56. Hubel DH, Wiesel TN: Receptive fields and functional architecture of monkey striate cortex. J Physiol (Lond)
1 9 5 : 2 1 5 - 2 4 3 , 1968
57. Wiesel TN, Hubel DH, Lam DMK: Autoradiographic demonstration of ocular-dominance columns in the monkey
striate cortex by means of transneuronal transport. Brain
Res 7 9 : 2 7 3 - 2 7 9 , 1974
58. Hubel DH, Wiesel TN: Sequence regularity and geometry
of orientation columns in the monkey striate cortex. J Comp
Neurol 158:267-294, 1974
59. Wiesel TN, Hubel DH: Ordered arrangement of orientation
columns in monkeys lacking visual experience. J Comp
Neurol 158:307-318, 1974
60. Hubel DH, Wiesel TN, LeVay S: Plasticity of ocular dominance columns in monkey striate cortex. Philos Trans R
Soc London [Biol] 2 7 8 : 3 7 7 - 4 0 9 , 1977
6 1 . LeVay S, Wiesel TN, Hubel DH: The development of ocular
dominance columns in normal and visually deprived monkeys. J Comp Neurol 191:1 - 5 2 , 1980
62. Cragg BG: The development of synapses in kitten visual
cortex during visual deprivation. Exp Neurol 4 6 : 4 4 5 - 4 5 1 ,
1975
6 3 . Rakic P: Prenatal development of the visual system in the
rhesus monkey. Phil Trans R Soc Lond [Biol] 2 7 8 : 2 4 5 260, 1977
64. Polyak S: The Vertebrate Visual System. In Kluver H (ed).
Chicago, IL, University of Chicago Press, 1957
65. Blake R, Hirsch HV: Deficits in binocular depth perception
in cats after alternating monocular deprivation. Science
190:1114-1116, 1975
66. Smith DC, Lorber R, Stanford LR, et al: Visual acuity following binocular deprivation in the cat. Brain Res 1 8 3 : 1 - 1 1 ,
1980
67. Freeman RD, Mellach R, Hartley S: Responsivity of normal
kitten striate cortex deteriorates after brief binocular deprivation. J Neurophysiol 4 5 : 1 0 7 4 - 1 0 8 4 , 1981
68. Ikeda H, Jacobson SG: Nasal field loss in cats reared with
convergent squint: Behavioral studies. J Physiol (Lond)
2 7 0 : 3 6 7 - 3 8 2 , 1977
69. Buisseret P, Imbert M: Visual cortical cells: Their developmental properties in normal and dark reared kittens. J
Physiol (Lond) 255 (2):511 - 5 2 5 , 1976
70. Fregnac Y, Imbert M: Early development of visual cortical
cells in normal and dark-reared kittens: Relationship between orientation selectivity and ocular dominance. J Physiol (Lond) 2 7 8 : 2 7 - 4 4 , 1978
7 1 . Cyander M, Chernenko G: Abolition of direction selectivity
in the visual cortex of the cat. Science 1 9 3 : 5 0 4 - 5 0 5 , 1 9 7 6
72. Leventhal AG, Hirsch HVB: Cortical effect of early selective
exposure to diagonal lines. Science 190:902-904, 1975
73. Movshon JA, Dursteler MR: Effects of brief periods of
unilateral eye closure on the kitten's visual system. J Neurophysiol 4 0 : 1 2 5 5 - 1 2 6 5 , 1977
74. Timney B, Mitchell DE, Cynader M: Behavioral evidence for
prolonged sensitivity to effects of monocular deprivation in
dark-reared cats. J Neurophysiol 4 3 : 1 0 4 1 - 1 0 5 4 , 1980
75. Daw NW, Berman NEJ, Ariel M: Interaction of critical periods in the visual cortex of kittens. Science 199:565-567,
1978
76. Banks MS, Aslin RS: Sensitive period for the development
of human binocular vision. Science 190:675-677, 1975
77. Blakemore C: The conditions required for the maintenance
of binocularity in the kitten's visual cortex. J Physiol (Lond)
2 6 1 : 4 2 3 - 4 4 4 , 1976
78. Blakemore C, Van Sluyters RC: Reversal of the physiological effects of monocular deprivation in kittens: Further
evidence for a sensitive period. J Physiol (Lond) 2 3 7 : 1 9 5 216, 1974
PHYSICAL THERAPY
PRACTICE
79. Movshon JA: Reversal of the physiological effects of monocular deprivation in the kitten's visual cortex. J Physiol
(Lond) 2 6 1 : 1 2 5 - 1 7 5 , 1976
80. Movshon JA: Reversal of the behavioral effects of monocular deprivation in the kitten. J Physiol (Lond) 2 6 1 : 1 7 5 187, 1976
8 1 . Mitchell DE, Cynader M, Movshon JA: Recovery from the
effects of monocular deprivation. J Comp Neurol 1 7 6 : 5 3 64, 1977
82. Kratz KE, Spear PD, Smith DC: Postcritical-period reversal
of effects of monocular deprivation on striate cortex cells in
the cat. J Neurophysiol 39:501 - 5 1 1 , 1 9 7 6
8 3 . Olson CR, Freeman RD: Monocular deprivation and recovery during sensitive period in kittens. J Neurophysiol
4 1 : 6 5 - 7 4 , 1978
84. Silverman MS, Clopton BM: Plasticity of binaural interaction: 1. Effect of early auditory deprivation. J Neurophysiol
40:1266-1274, 1977
85. Clopton BM, Silverman MS: Plasticity of binaural interaction: 2. Critical period and changes in midline response. J
Neurophysiol 40:1275-1280, 1977
86. Riesen AH: Stimulation as a requirement for growth and
function in behavioral development. In Fiske DW, Maddi SR
(eds): Functions of Varied Experience. Homewood, IL. Dorsey Press, 1961, pp 5 7 - 1 0 5
96. Mommaerts WFHM, Seraydarian K, Suh M, et al: The conversion of some biochemical properties of mammalian skeletal muscles following cross-reinnervation. Exp Neurol
55:637-653, 1977
97. Barany M, Close RI: The transformation of myosin in the
cross-innervated rat muscles. J Physiol (Lond) 2 1 3 : 4 5 5 474,1971
98. Weeds AG, Trenthan DR, Kean CJC, et al: Myosin from
cross-reinnervated cat muscles. Nature 247:135-139,
1974
99. Miledi R, Stefani E, Zelena J: Neural control of acetylcholine-sensitivity in rat muscle fibres. Nature 220:497-498,
1965
100. Sreter FA, Luff AR, Gergely J: Effect of cross-reinnervation
on physiological parameters and on properties of myosin
and sarcoplasmic reticulum of fast and slow muscles of the
rabbit. J Gen Physiol 66:811-822, 1975
101. Mommaerts WFHM, Butler AJ, Seraydarian K: The modification of some biochemical properties of muscle by crossinnervation. Proc Natl Acad Sci 64:128-133, 1969
102. Ellisman MH, Brooke MH, Kaiser KK, et al: Appearance in
slow muscle sarcolemma of specializations characteristic
of fast muscle after reinnervation by a fast muscle nerve.
Exp Neurol 58:59-67, 1978
Effects of Disrupting A x o p l a s m i c Flow
EFFECTS OF EXPERIENCE ON MOTOR
DEVELOPMENT
87. Buller AJ, Eccles JC, Eccles RM: Differentiation of fast and
slow muscles in the cat hindlimb. J Physiol (Lond) 150:399416, 1960
88. Kelly AM, Rubinstein NA: Why are fetal muscles slow?
Nature 288:266-269, 1980
Effects of Cross-Reinnervation
89. Buller AJ, Eccles JC, Eccles RM: Interactions between
motoneurons and muscles in respect of the characteristic
speeds of their responses. J Physiol (Lond) 150:417-439,
1960
90. Lewis DM, Kean CJC, McGarrick JD: Dynamic properties
of slow and fast muscle and their trophic regulation. In
Drachman DB (ed): Trophic Functions of the Neuron. Ann
NY Acad Sci 228:105-120, 1974
9 1 . Close R: Dynamic properties of mammalian skeletal muscle.
Physiol Rev 52:129-197, 1972
92. Guth L, Samaha FJ, Albers RW: The neural regulation of
some phenotypic differences between the fiber types of
mammalian skeletal muscle. Exp Neurol 2 6 : 1 2 6 - 1 3 5 , 1 9 7 0
9 3 . Samaha FJ, Guth L, Albers W: The neural regulation of
gene expression in the muscle cell. Exp Neurol 2 7 : 2 7 6 284, 1970
94. Prewitt MA, Salafsky B: Effect of cross innervation on
biochemical characteristics of skeletal muscles. Am J Physiol 213:295-300, 1967
95. Prewitt MA, Salafsky B: Enzymic and histochemical
changes in fast and slow muscles after cross-innervation.
Am J Physiol 218:69-74, 1970
Volume 62 / Number 8, August 1982
103. Dahlstrom A: Effect of colchicine on transport of amine
storage granules in sympathetic nerves of rat. Eur J Pharmacol 5:111-113, 1968
104. Kreutzberg GW: Neuronal dynamics and axonal flow: 4.
Blockage of intra-axonal enzyme transport by colchicine.
Proc Natl Acad Sci 62:722-728, 1969
105. Albuquerque EX, Warnick JE, Tasse JR, et al: Effects of
vinblastine and colchicine on neural regulation of the fast
and slow skeletal muscles of the rat. Exp Neurol 37:607,
1972
106. Albuquerque EX, Warnick JE, Sansone FM, et al: The
effects of vinblastine and cholchicine on neural regulation
of muscle. Annals of NY Acad Sci 228:224-243, 1974
107. Hofmann WW, Peacock JH: Postjunctional changes induced by partial interruption of axoplasmic flow in motor
nerves. Exp Neurol 41:345-356, 1973
108. Drachman DB: The role of acetylcholine as a neurotrophic
transmitter. Ann NY Acad Sci 228:160-175, 1974
109. Lomo T: Neurotrophic control of colchicine effects on muscle. Nature 249:473-474, 1974
Effects of Muscle Activity
110. Salmons S, Vrbova G: The influence of activity on some
contractile characteristics of mammalian fast and slow muscles. J Physiol (Lond) 201:535-549, 1969
111. AI-Amood WS, Buller AJ, Pope R: Long-term stimulation of
cat fast-twitch skeletal muscle. Nature 244:225-227, 1973
112. Sreter FA, Gergely J, Salmons S, et al: Synthesis by fast
muscle of myosin light chains characteristic of slow muscle
in response to long-term stimulation. Nature New Biology
241:17-18, 1973
1143