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results suggest that synapse elimination in Layer IV
proceeds in the absence of visually evoked activity, the
reason for it is not clear. One possibility is that spon-
taneous activity within corticothalamic curcuits that is
independent of visual input has an impact on synapse
development, as discussed below.
A very direct measure of synaptic pruning was
achieved by imaging individual retinal ganglion cell
(RGC) arbors as they compete for postsynaptic space
within the frog optic tectum (Ruthazer et al., 2003).
When RGC axons from both eyes are induced to inner-
vate the same tectal lobe, the axons compete for post-
synaptic space and gradually segregate from one
another (Figure 9.12A). A single ipsilateral RGC was
labeled with a fluorescent dye during this period of
segregation, and imaged over an eight-hour period.
The addition and retraction of each axonal branch was
followed during this interval (Figure 9.12B). The brain
was then fixed, and RGC projections from each eye
were bulk-labeled with two different dyes. The proce-
dure permitted one to characterize the innervation
density of each eye, a measure that is analogous to
ocular dominance. New branches that persist for the
entire recording period, called stabilized branches , are
more numerous when formed in a tectal region domi-
nated by the same eye (Figure 9.12C). Conversely, RGC
axons preferentially retract branches from territory
that is already dominated by the other eye. This mech-
anism was eliminated in the presence of an antagonist
to a class of glutamate receptors called NMDA re-
ceptors (see below). This result shows that branch
addition and retraction (and presumably synapse for-
mation and elimination) can occur simultaneously and
depend on synaptic transmission.
The majority of binocular neurons in the cortex are
created by local projections from one cortical neuron
to its neighbors, and these projections also become
refined during development. Since neurons in all
layers of the cortex are monocular following strabis-
mus, it would be interesting to know what happens to
these intracortical projections. Do they now become
more segregated than normal, extending the striped
pattern throughout the entire cortical depth? This
seems to be precisely what happens. Small injections
of dye were made in the cortex, retrogradely labeling
neurons that form local projections to this area (Figure
9.13). The animals were also injected with 2-deoxyglu-
cose (see BOX: Watching Neurons Think) and stimu-
lated through one eye to label all areas of cortex that
were driven by that eye. With this double-labeling
technique, one can learn whether local projection
neurons are found exclusively above one ocular dom-
inance column or both. In normal animals, the local
projections come from both columns, and the cells that
they innervate are binocularly driven. In strabismic
cats, the local projections originate exclusively above
one column (Löwel and Singer, 1992). Furthermore,
this alteration of horizontal projections occurs very
rapidly; after only two days of strabismus, one can
detect the loss of horizontal projections (Trachtenberg
and Stryker, 2001). Thus, activity influences the devel-
opment of synaptic connections not only in ascending
sensory projections, but also in many of the intracorti-
cal projections.
The central concept to emerge from these studies is
that coactive synapses are stabilized, while inactive
synapses, particularly those that are inactive while
others are firing, become weakened and in many cases
are eliminated. As one might expect, the development
of a complicated structure such as the cortex is unlikely
to be explained by one tidy hypothesis. We have just
learned that activity-dependent changes in connectiv-
ity are occurring simultaneously at several locations.
Functional and structural changes are also found in the
LGN following lid suture or strabismus, and the extent
to which these changes influence cortical development
is not clear. Proprioceptive feedback from the eye
muscles also contributes, and its blockade somehow
prevents monocular deprivation from altering synap-
tic connections in the cortex. This is not to lose sight of
the forest, but rather to say that there are some large
trees that must be carefully examined.
Given the great complexity of cortex circuitry, it
would be nice to have a simpler model system for
synaptic plasticity. As we learned in the last chapter,
the neuromuscular junction (NMJ) is the most accessi-
ble and well studied of all synapses, and it has served
as the mascot of synaptic plasticity for decades. In
mammals, there is only a single type of synapse on fast
muscle fibers, and only a single fiber ends up inner-
vating each muscle cell in adults (above). If that were
not good enough, it is also extremely easy to record
intracellularly from muscle cells, to manipulate the
nerve or muscle cells, and to place the entire system in
tissue culture. Of course, these advantages also serve
as the limitations. For example, there are no inhibitory
synapses, and the postsynaptic cell does not have den-
drites or spines, as found in many areas of the central
nervous system.
Despite these differences, it is uncanny how much
NMJ developmental plasticity resembles that observed
in cortex. As we learned earlier, mammalian muscle
cells are innervated by more than one axon at birth, but
after synapse elimination only a single axon remains.
When action potentials are blocked with TTX during
the normal period of synapse elimination, muscle
cells remain polyneuronally innervated (Figure 9.14)
(Thompson et al., 1979). The same kind of results are
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