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most effective retinal ganglion cell is activated, it will
cause the tectal neuron to fire an action potential. Thus,
any retinal ganglion cell that produces a subthreshold
event within the next 20 ms may become depressed
and subject to elimination.
and become inserted into the postsynaptic membrane
within 10 minutes of stimulation (Shi et al., 1999).
Eye opening is associated with an increase in the per-
centage of “silent” NMDAR synapses in the rat supe-
rior colliculus. Furthermore, the AMPAR : NMDAR
ratio increases during the next 24 hours of vision, and
there is a commensurate reduction in the number
of retinal inputs per postsynaptic neuron (Lu and
Constantine-Paton, 2004). A similar observation was
made in the optic tectum of developing tadpoles. When
retinal afferents are stimulated electrically, most imma-
ture synapses do not exhibit a postsynaptic response if
the cell is held near the resting potential. However, if the
cell is depolarized to + 55 mV, then the synapses imme-
diately display a response. This is because the NMDAR
is now able to open when bound by glutamate. As the
synapses mature in this system, they begin to express a
greater number of AMPA-type glutamate receptors.
Furthermore, constitutive expression of CaMKII accel-
erates this transition (Wu et al., 1996). Thus, CaMKII
may serve as an activity-dependent mechanism for
strengthening some synapses by recruiting functional
AMPARs, while eliminating others.
Tw o experiments suggest that glutamate receptor
turnover and modification are controlled by electrical
activity. When primary cultures of spinal neurons are
grown in the presence of the glutamate receptor block-
ers, CNQX, a greater number of AMPA receptor sub-
units accumulate at synaptic contacts and spontaneous
EPSCs are larger. Conversely, when excitatory synap-
tic activity is increased by growing the cultures in
GABA and glycine receptor antagonists, the amount of
synaptic AMPA receptors declines and spontaneous
EPSCs are smaller (O'Brien et al., 1998). Apparently,
synaptic transmission controls the number of synaptic
AMPA receptors by regulating the half-life of the
receptor subunits.
The ability of synapses to linger on, even though
they provide little input to the postsynaptic cell, may be
due to the presence of trophic substances. For example,
when glial cell line-derived neurotrophic factor
(GDNF) is overexpressed in the muscle cells of trans-
genic mice, the number of motor neuron terminals at
each endplate is dramatically increased (Nguyen et al.,
1998). The neurotrophin, BDNF, prolongs the multiple
innervation of mammalian muscle cells in vivo, and
this effect is far more prominent when assessed
anatomically. At postnatal day 12, almost 80% of
muscle cells are contacted by more than one nerve
terminal, yet only about 25% of muscle cells display
multiple EPSP amplitudes (as assessed with the proce-
dure shown in Figure 9.2). This result suggests that
many of the extramotor terminals must be functionally
silent (Kwon and Gurney, 1996). Thus, synapse elimi-
An extreme case of synaptic potentiation occurs
when the physical contacts between nerve cells dis-
play absolutely no transmission, yet can be turned on
by using them. These “silent synapses” have been
observed in both young and adult animals. For
example, inactive contacts have been observed in cul-
tures of chick ciliary ganglion neurons and myotubes.
Only 58% of the contacts are functional, even though
the myotubes are expressing plenty of AChRs (Dubin-
sky and Fischbach, 1990). When cAMP levels are
increased in the cultures, 93% of contacts are functional,
suggesting that “silent” presynaptic terminals are acti-
vated by a cAMP signaling pathway. Similarly, silent
presynaptic terminals in the neonatal hippocampus can
be turned on by activating AChRs (Maggi et al., 2003).
The enhancement of synaptic transmission that is
observed soon after innervation may also occur if
existing receptors on the postsynaptic membrane are
modified. When embryonic rat medullary neurons are
placed in dissociated culture, there is no indication
of glycine-evoked currents during the first six days
in vitro. However, glycine-evoked currents can be
observed in excised patches of membrane within a day
of plating. This result suggests that the glycine recep-
tors are initially “silent” and are converted to an active
state during development (Lewis et al., 1990).
It is possible that many glutamatergic synapses
are silent during development because activation of
the NMDAR requires membrane depolarization
(Figure 9.27A). Intracellular recordings from the
neonatal hippocampus show that most synapses have
only NMDARs, and they do not respond when mem-
brane potential is held at -60 mV. However, neural
activity can enhance synaptic transmission by rapidly
recruiting new functional AMPA-type glutamate
receptors (Durand et al., 1996). The appearance of
functional AMPARs may be due to either insertion or
modification. For example, the phosphorylation state
of AMPA-type glutamate receptors can be modified by
NMDAR activity, leading to the dephosphorylation of
a particular AMPA-type glutamate receptor, called
GluR1. When this happens, excitatory synaptic trans-
mission is depressed (Lee et al., 1998). Alternatively,
glutamate receptors can be moved from the cytoplasm
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