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motility increases (Figure 9.32C). The results suggest
that dendrites are maximally sensitive to synaptic
activity during this period and that they participate in
the activity-dependent formation and elimination of
synaptic connections (Majewska and Sur, 2003).
As with cell death, the effect of synaptic transmis-
sion can be tested directly by manipulations that block
glutamate receptors. When chick embryos are treated
with an NMDA receptor antagonist, cerebellar Purk-
inje cell dendrites do not develop as many branches
and occupy a smaller cross-sectional area (Vogel and
Prittie, 1995). A similar effect has been observed in frog
optic tectal neurons and in spinal motor neurons. In
hippocampal cultures, the number of dendritic spines,
but not the number of branches, is dependent on glu-
tamatergic synaptic activity (Kossel et al., 1997). The
effects of excitatory transmission can change during
development as new signaling systems are added to
the cytoplasm. For example, the decrease in the growth
of optic tectum dendrites correlates with increased
expression of CaMKII, and the rate of growth is ex-
perimentally increased when animals are treated with a
CaMKII inhibitor (Wu and Cline, 1998). It is also likely
that other growth-promoting factors are co-released
with neurotransmitter. In organotypic cultures of
visual cortex, function-blocking antibodies against the
TrkB receptor decrease the amount of basal dendritic
growth, indicating that endogenously released BDNF
promotes postsynaptic growth (McAllister et al., 1997).
Spine morphology is controlled by the cytoskeletal
component, actin, which is highly dynamic in develop-
ing systems (Star et al., 2002). Glutamatergic synaptic
activity can influence actin polymerization and stabi-
lize spines by raising intracellular calcium (Fischer et
al., 2000). In fact, dendrite stability is very sensitive to
local calcium levels. In the embryonic chick retina, den-
dritic retractions can be prevented by locally raising
calcium levels within the process (Lohmann et al.,
2002). A local rise in calcium may serve to stabilize actin
filaments, perhaps by activating gelsolin, the calcium-
dependent actin-binding protein. In general, GTP-
binding proteins (Rho GTPases) have been implicated
in regulating neuron morphology by affecting the sta-
bility and assembly of actin filaments (Luo, 2002).
Given that the effects of excitatory denervation are
so dramatic, it would be surprising if inhibitory
synapses did not have a trophic influence on postsy-
naptic maturation. In fact, inhibitory terminals appear
to have the opposite effect of excitatory terminals in a
central auditory nucleus, the lateral superior olive
(LSO). Neurons in the LSO can be selectively deprived
of functional inhibition by removal of the contralateral
cochlea, and this manipulation leads to a significant
increase in dendritic branching. Furthermore, when
organotypic cultures of the LSO are grown in the pres-
ence of the inhibitory antagonist, strychnine, dendrites
are twice as long as those grown in normal media
(Sanes et al., 1992; Sanes and Hafidi, 1996). Thus,
synaptic terminals do not provide a uniform signal to
growing dendrites.
At one level, the purpose of synapse elimination
seems perfectly obvious: to create the optimal connec-
tions between neurons based upon their use. Perhaps
the nervous system cannot take full advantage of the
plasticity mechanisms unless it generates extra cell
bodies, a surplus of dendritic branches, and a profu-
sion of presynaptic arbors. In reality, the purpose of
synapse elimination will remain enigmatic until we
can produce a specific alteration in a single set of adult
connections, let's say two climbing fibers per Purkinje
cell, and determine the exact behavioral outcome.
Therefore, our understanding of developmental plas-
ticity is intimately tied to our insight into how the CNS
encodes sensory information and controls movement.
What is the optimal pattern of connectivity for
running, singing, perfect pitch, speed reading, learn-
ing, and so forth? Is it even possible to have a nervous
system that is optimized for diverse motor, sensory,
and cognitive tasks? Unfortunately, we have yet to
devise an experiment that tests whether extra cell
bodies or small arborization errors actually affect
animal behavior.
At present, we believe that synapses can be weak-
ened or lost if they are not activated correctly during
development. This might be particularly important for
animals, such as humans, that inhabit a wide range of
environments. For example, it is likely that our central
auditory system is shaped by the spoken language(s)
to which we are exposed as infants (see Chapter 10).
However, the experiments that demonstrate an influ-
ence of environment or neural activity itself have
remained rather flagrant. For example, it is unlikely
that any animal sees only vertical stripes during devel-
opment. Yet, we know that developing humans do
experience many “extreme” rearing environments,
such as blindness, deafness, malnutrition, and many
others that result from genetic or epigenetic causes.
Therefore, the clinical importance of understanding
developmental plasticity is enormous.
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