Neuron
Volume 100, Issue 1, 10 October 2018, Pages 106-119.e7
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Article
Differential Nanoscale Topography and Functional Role of GluN2-NMDA Receptor Subtypes at Glutamatergic Synapses

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Highlights

  • NMDARs are organized in nanodomains within hippocampal synapses

  • GluN2A- and GluN2B-NMDARs are differentially organized at the nanoscale level

  • GluN2A- and GluN2B-NMDARs nanodomains are regulated through different pathways

  • GluN2A- and GluN2B-NMDARs relative ratio bi-directionally regulates LTP

Summary

NMDA receptors (NMDARs) play key roles in the use-dependent adaptation of glutamatergic synapses underpinning memory formation. In the forebrain, these plastic processes involve the varied contributions of GluN2A- and GluN2B-containing NMDARs that have different signaling properties. Although the molecular machinery of synaptic NMDAR trafficking has been under scrutiny, the postsynaptic spatial organization of these two receptor subtypes has remained elusive. Here, we used super-resolution imaging of NMDARs in rat hippocampal synapses to unveil the nanoscale topography of native GluN2A- and GluN2B-NMDARs. Both subtypes were found to be organized in separate nanodomains that vary over the course of development. Furthermore, GluN2A- and GluN2B-NMDAR nanoscale organizations relied on distinct regulatory mechanisms. Strikingly, the selective rearrangement of GluN2A- and GluN2B-NMDARs, with no overall change in NMDAR current amplitude, allowed bi-directional tuning of synaptic LTP. Thus, GluN2A- and GluN2B-NMDAR nanoscale organizations are differentially regulated and seem to involve distinct signaling complexes during synaptic adaptation.

Keywords

glutamate receptor
dSTORM
single molecule
GluN2 subunit
synapse

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