Healthcare and Medicine Reference
In-Depth Information
phospholipase (PLC) signaling pathway. In mice that
are deficient in a specific isoform, PLCb4, climbing
fiber elimination is impaired in the rostral portion of
the cerebellum where the mRNA for PLCb4 is pre-
dominantly expressed (Kano et al., 1998). Therefore,
synapse elimination may involve the collaboration of
more than one type of glutamate receptor and intra-
cellular signaling cascade.
It is likely that transmitters besides ACh are
released at the nerve-muscle junction and that they
play an important role in synapse maturation and plas-
ticity. For example, the neurotrophins, BDNF and
NT-4 are expressed at the NMJ, and AChR clusters
are rapidly lost when TrkB signaling is disrupted
(Gonzalez et al., 1999; Wells et al., 1999). A second
protein, calcitonin gene-related peptide (CGRP), is
present at the developing nerve-muscle junction and
may participate in the competition for postsynaptic
space (Nelson et al., 2003). CGRP is known to upregu-
late AChR synthesis (New and Mudge, 1986). Fur-
thermore, activation of the CGRP receptor can elevate
postsynaptic cAMP, leading to activation of PKA and
phosphorylation of AChRs (Miles et al., 1989; Lu et al.,
1993). Therefore, it is possible that active motor nerve
terminals use CGRP to recruit the protective influence
of PKA signaling (Figure 9.25C).
Neuromodulatory transmitters have also been
shown to affect synaptic plasticity during develop-
ment. For example, the effects of monocular depriva-
tion are markedly reduced when either cholinergic or
noradrenergic or serotonergic terminals are eliminated
from the developing nervous system, although none of
these afferents mediates visually evoked activity in the
cortex (Kasamatsu and Pettigrew, 1976; Bear and
Singer, 1986; Gu and Singer, 1995). Apparently, the pro-
jections from certain brainstem nuclei (e.g., the raphe,
the locus coeruleus, and the nucleus basalis) arborize
widely in the brain, and can modify synaptic transmis-
sion in adult and developing animals. It is still unclear
how these modulatory systems are activated during
development or how they interact with the primary
afferent transmitter system. However, such findings do
suggest that our concept of synaptic plasticity in the
central nervous system is still rather rudimentary.
ment. For example, bursts of high-frequency stimula-
tion delivered to retinal afferents produce an enhance-
ment of excitatory synaptic transmission in 40% of
LGN neurons tested (Mooney et al., 1993). Moreover,
a NMDAR antagonist is able to block this activity-
dependent potentiation of synaptic transmission in
most neurons. This phenomenon was called long-term
potentiation (LTP) when it was first discovered in adult
tissue (see BOX: Remaining Flexible).
LTP has been found at many other developing
synapses, although it is most prominent in the cortex
and hippocampus. One possibility is that LTP is an
important mechanism in the adult nervous system and
simply appears during development without playing
any particular role in synaptogenesis. However, LTP is
particularly prominent during development in some
areas of the cortex (Figure 9.29A). For example, LTP
has been studied at synapses between thalamic affer-
ents and somatosensory “barrel” cortex, and it is only
found before postnatal day 7 (Crair and Malenka,
1995). There are also suggestions that it determines
which synaptic connections will drive the postsynap-
tic neuron most effectively. LTP is found in two differ-
ent forebrain nuclei (LMAN and area X) that are
required for vocal learning in developing zebra finches
(Boetigger and Doupe, 2001; Ding and Perkel, 2004).
Interestingly, each form of LTP is restricted to a par-
ticular developmental period, occurring earlier within
LMAN and later within area X.
If an LTP mechanism helps to shape the connectiv-
ity between neurons during development, then it
should selectively strengthen the active input, and not
the inactive one. To test this idea, whole cell recordings
were obtained from Xenopus tectal neurons in vivo.
Small extracellular stimulating electrodes were placed
at two positions in the retina that project retinal gan-
glion cell (RGC) axons to the recorded tectal neuron,
and electrical stimulation evoked EPSCs (Tao et al.,
2001). In young tadpoles, stimulation of one RGC leads
to an enhanced excitatory postsynaptic response for
both inputs. That is, there is no specificity. In contrast,
when a single RGC is stimulated in slightly older
tadpoles, it subsequently displays LTP, whereas the
synaptic connection from the unstimulated RGC is
unchanged. Dendritic growth and calcium regulation
may account for this difference between ages. Synap-
tic stimulation elicits a rise in postsynaptic calcium
throughout the younger tectal neurons, but the
calcium rise is highly restricted in the older age group.
These findings emphasize, once again, that synaptic
plasticity is very restricted in the spatial domain
(Figures 9.23 and 9.26).
Synaptic activity can also lead to a long-lasting
decrease in EPSP amplitude, often called long-term
GAIN CONTROL
To this point, our discussion has focused on the
concept that synapses can be weakened and elimi-
nated by the activity of neighboring connections.
However, synaptic transmission can also undergo
long-lasting alterations in strength during develop-
Search Pocayo ::




Custom Search