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synaptic transmission appears to be absent because
most synapses have only functional NMDARs, and
NMDA receptors tend to remain closed at the resting
membrane potential. These are sometimes referred to
as “silent synapses.” When NMDARs are permitted to
be active by stimulating the synapse during depolariz-
ing current pulses, the synapses are soon found to have
functional AMPARs (Durand et al., 1996). A similar
pattern of maturation occurs in the optic tectum of
Xenopus tadpoles. When calcium-calmodulin-depend-
ent protein kinase II (CaMKII) is constitutively
expressed in the tectal neurons, the appearance of
AMPAergic transmission can be facilitated. This sug-
gests that calcium entry through NMDARs may acti-
vate CaMKII, which mediates the recruitment of
functional AMPARs (Wu et al., 1996). Activation of
“silent” synapses has also been observed at slightly
later periods of development and may, in fact, underlie
certain forms of learning or memory (see Chapter 9).
The time that the neurotransmitter remains in the
synaptic cleft will also affect the duration of synaptic
potentials, and the development of transmitter uptake
systems is criticial for the emergence of mature func-
tion. Neurotransmitter transporter protein develop-
ment has been studied by expressing polyadenylated
brain RNA (polyadenylation, or the addition of about
200 adenylate residues, is a common modification to
transcripts in eukaryotic cells) in Xenopus oocytes
(Blakely et al., 1991). Messenger RNA was obtained
from animals of different ages and placed in a Xenopus
oocyte expression system. The amount of transport
was quantified by incubating the oocyte in a radiola-
beled amino acid neurotransmitter, such as 3 H-glycine,
and the amount of 3 H was quantified with a liquid
scintillation counter. By using this assay, it was found
that glutamate and GABA transporters first appear
in the cortex at postnatal day 3 and increase to
adult levels over the next two weeks. In the brainstem,
the expression of a glycine transporter gradually
increases to adult levels over the first three postnatal
A number of amino acid transporters have now been
identified at the molecular level, and a few studies have
traced their developmental appearance using in situ
hybridization. The excitatory amino acid transporters,
mEAAT1 and mEAAT2, are first found in the prolifer-
ative zone of mouse forebrain and midbrain during
FIGURE 8.31 The NMDA-type glutamate receptors close more
rapidly with age. A. Intracellular recordings were obtained from rat
hippocampal neurons in a brain slice preparation, and AMPA-type
glutamate receptors and GABA receptors were blocked. Thus, stim-
ulation of afferents evoked glutamate release, and only postsynap-
tic NMDA-type receptors were activated. B. The afferent-evoked
EPSPs were longer lasting in neurons from young neurons due to
the slow decay time. (Adapted from Hestrin, 1992)
The signals that are responsible for receptor transi-
tions may come from neurotransmission itself. For
example, the waning of NMDAR-mediated responses
in many areas of the brain (see above) is often accom-
panied by increased transmission through a second
class of glutamate receptors, called AMPA receptors .
Functional AMPARs can be rapidly recruited by
NMDAR activity. In the neonatal rat, glutamatergic
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