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gliogenesis (E15-E19). However, mEAAT2 mRNA con-
tinues to increase in many areas of the CNS during the
first two to three postnatal weeks (Sutherland et al.,
1996). Transcripts for the Na + /Cl - -dependent glycine
transporter (GlyT1), found almost exclusively in glial
cells, achieve maximal levels in E13 mice, much earlier
in neural development (Adams et al., 1995). Although
the presence of transporter mRNA suggests that neu-
rotransmitter could be efficiently cleared at the onset of
synaptogenesis, studies of amino acid transporter
function show that their physiology remains immature
for some time (Blakely et al., 1991). Therefore, the mat-
uration of transporter proteins probably limits the
kinetics of synaptic transmission.
SHORT-TERM PLASTICITY
To this point we have considered only the most
basic response of a synapse: the release of transmitter
to a single action potential and the postsynaptic
current that it produces. Of course, neurons will fire
many times per second under realistic conditions, and
the synaptic response may become facilitated or
depressed over time. These changes in synaptic
response are called short-term plasticity, and their
maturation depends on the development of presynap-
tic release properties and the complement of postsyn-
aptic receptors and ion channels.
A simple approach to examine short-term plasticity
involves taking relatively thick (300-500 mm) slices of
brain tissue at increasing postnatal ages and recording
the synaptic response that is elicited when trains of
stimuli are delivered to the afferent pathway. To
examine short-term plasticity, synaptic currents were
recorded from MNTB neurons in response to stimula-
tion of excitatory afferents from the cochlear nucleus
(see schematic in Figure 8.28A). MNTB neurons are
innervated by only a single glutamatergic afferent that
makes a large synapse on the cell body, called the
endbulb of Held . When these synapses are stimulated at
200 Hz in young MNTB neurons (P5), they display a
rapid depression of the postsynaptic response, and
there are complete failures where the transmitter is
apparently not released by the endbulb of Held (Figure
8.32A). However, when the same stimulus is delivered
to MNTB neuron afferents at P14, the response does
not display as much depression, and there are no fail-
ures of transmitter release (Joshi and Wang, 2002).
Several mechanisms may account for this maturation.
In young animals, the endbulb of Held produces an
action potential that lasts a relatively long time, and
this prevents it from responding to each stimulus. It is
FIGURE 8.32 Development of short-term synaptic plasticity. A.
AMPA receptor-mediate EPSCs are recorded in MNTB neurons in
response to a 200 Hz stimulus train. Examples are shown from
neurons at P5, P9, and P14. There is a significant reduction in the
extent of synaptic depression and failures. B. EPSPs are recorded in
Layer 5 pyramidal neurons in response to stimulation of a second
Layer 5 cell. In P14 cortex, stimulation of the presynaptic neuron at
an increasing rate (responses to 10, 20, and 40 Hz are shown) evoked
EPSPs that declined in amplitude. In P28 cortex, stimulation of a
presynaptic Layer 5 neuron evoked EPSPs in a postsynaptic Layer
5 cell that facilitated at that same stimulus rates. The graph shows
summary data from P14 ( n = 52), P18 ( n = 9), P22 ( n = 6), and P28
( n = 10) rats. (From Reyes and Sakmann, 1999; Joshi et al., 2002)
also likely that the pool of vesicles available for release
during rapid stimulation increases with development.
Postsynaptic mechanisms could also contribute to this
depression, including desensitization of glutamate
receptors.
The developing cortex displays an even greater
transformation in short-term plasticity (Figure 8.32B).
When two interconnected neurons are recorded in
P14 sensorimotor cortex, it is found that excitatory
synapses display a depression when stimulated
between 10 and 40 Hz. When a similar pair of neurons
is recorded at P28, the excitatory connections display
facilitation (i.e., the second postsynaptic response is
larger than the first) (Reyes and Sakmann, 1999). Once
again, the developmental switch from depression to
facilitation may be caused by several factors including
regulation of presynaptic Ca +2 concentration and glu-
tamate receptor desensitization.
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