Activity-dependent control of NMDA receptor subunit composition at hippocampal mossy fibre synapses.
J Physiol. 2018-01-30; 596(4): 703-716
DOI: 10.1113/jp275226
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KEY POINTS: CA3 pyramidal cells display input-specific differences in the subunit
composition of synaptic NMDA receptors (NMDARs). Although at low density, GluN2B
contributes significantly to NMDAR-mediated EPSCs at mossy fibre synapses.
Long-term potentiation (LTP) of NMDARs triggers a modification in the subunit
composition of synaptic NMDARs by insertion of GluN2B. GluN2B subunits are
essential for the expression of LTP of NMDARs at mossy fibre synapses.
ABSTRACT: Single neurons express NMDA receptors (NMDARs) with distinct subunit
composition and biophysical properties that can be segregated in an
input-specific manner. The dynamic control of the heterogeneous distribution of
synaptic NMDARs is crucial to control input-dependent synaptic integration and
plasticity. In hippocampal CA3 pyramidal cells from mice of both sexes, we found
that mossy fibre (MF) synapses display a markedly lower proportion of
GluN2B-containing NMDARs than associative/commissural synapses. The mechanism
involved in such heterogeneous distribution of GluN2B subunits is not known. Here
we show that long-term potentiation (LTP) of NMDARs, which is selectively
expressed at MF-CA3 pyramidal cell synapses, triggers a modification in the
subunit composition of synaptic NMDARs by insertion of GluN2B. This
activity-dependent recruitment of GluN2B at mature MF-CA3 pyramidal cell synapses
contrasts with the removal of GluN2B subunits at other glutamatergic synapses
during development and in response to activity. Furthermore, although expressed
at low levels, GluN2B is necessary for the expression of LTP of NMDARs at MF-CA3
pyramidal cell synapses. Altogether, we reveal a previously unknown
activity-dependent regulation and function of GluN2B subunits that may contribute
to the heterogeneous plasticity induction rules in CA3 pyramidal cells.