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units, particularly the e-subunit (Figure 8.27B) (Harris
et al., 1988; Martinou et al., 1991). Mice deficient for
NRG1 or ErbB2 die prior to muscle formation and the
influence on synaptogenesis cannot be determined.
However, the heterzygotes of a NRG1 knockout mouse
express less neuregulin than controls, and display a
significant reduction of AChRs (Sandrock et al., 1997).
This was studied by measuring the size of individual
synaptic events, called quanta , which are probably due
to the release of ACh from a single synaptic vesicle.
These quantal events are smaller in heterozygote mice,
presumably because there is less AChR to transduce
the signal. Similarly, when erbB2 is inactivated selec-
tively in muscle, there is a modest decline in miniature
endplate currents and in AChR number at the synapse
(Leu et al., 2003).
Unfortunately, the NRG-erbB signaling pathway is
also essential to Schwann cell survival, and Schwann
cell-derived cues are not available to the motor axons.
Furthermore, muscle cells contain and release NRG1,
which can induce AChR gene expression (Meier et al.,
1998; Yang et al., 2001). Finally, a second neuregulin
(NRG2) is expressed by motor neurons and Schwann
cells and is found at the neuromuscular junction
(Rimer et al., 2004). Despite these complications, most
evidence suggests that NRG regulates postsynaptic
transcription.
Several members of the NRG and erbB families
are found in the chick and mammalian CNS during
development, suggesting a role in neuron-neuron
synapse formation. In developing chick sympa-
thetic ganglia, a specific NRG1 isoform (type III) selec-
tively upregulates the transcription of the a3 AChR
subunit (Yang et al., 1998). In the developing cerebel-
lum, NRG1 has been shown to increase the expression
of an NMDA receptor subunit and a GABA A recetor
subunit (Ozaki et al., 1997; Rieff et al., 1999). Intrest-
ingly, NRG1 has been shown to decrease GABA A recep-
tor expression in the hippocampus without affecting
glutamate receptors (Okada and Corfas, 2004).
A
Excitatory synapse
(EPSP)
Inhibitory synapse
(IPSP)
K +
glycine
Cochlear
Nucleus
Na +
Cochlear
Nucleus
Cl -
glutamate
LSO
MNTB
Excitatory
pathway
Inhibitory
pathway
P1
EPSP
IPSP
20 mV
P11
20 ms
EPSP
IPSP
B
P20
100
EPSP
IPSP
50
**
0
0
5
10
15
17-23
(mean)
Postnatal day
MATURATION OF TRANSMISSION AND
RE CEPTOR ISOFORM TRANSITIO NS
FIGURE 8.28 The duration of synaptic potentials decreases
during development. A. A schematic of a central auditory nucleus,
the lateral superior olive (LSO), that receives excitatory synapses
from the ipsilateral cochlear nucleus and inhibitory synapses from
the medial nucleus of the trapezoid body (MNTB). The inset at left
shows that excitatory terminals release glutamate and open recep-
tors that are permeable to Na + and K + . The inset at right shows that
inhibitory terminals release glycine and open receptors that are per-
meable to Cl - . B. When intracellular recordings are made from LSO
neurons during the first three postnatal weeks, the afferent-evoked
EPSP and IPSP durations decline by about 10-fold. Examples for
postnatal day 1, 11, and 20 are shown at the top, and a summary of
all IPSPs is plotted in the graph. (Adapted from Sanes, 1993)
Synapse formation is rapid, but adult functional
properties emerge only gradually during develop-
ment. One of the most common observations is that the
duration of excitatory or inhibitory synaptic potentials
declines over the course of days (Figure 8.28). For
example, in the rat neocortex, the duration of excita-
tory postsynaptic potentials (EPSPs) decreases from
approximately 400 to 100 ms during the first two post-
 
 
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