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Nanoscale change in the synapse, Macroscopic changes! - Neuron 2018

Nanoscale change in the synapse, Macroscopic changes! - Neuron 2018

Differential nanoscale topography and functional role of GluN2-NMDA receptor subtypes at glutamatergic synapses

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.

Kellermayer B, Ferreira JS, Dupuis J, Levet F, Grillo-Bosch D, Bard L, Linarès-Loyez J, Bouchet D, Choquet D, Rusakov DA, Bon P, Sibarita JB, Cognet L, Sainlos M, Carvalho AL, Groc L

Leg. The nanometric organization of NMDA receptors regulates the plasticity of synapses. (A) Distribution of NMDA receptors on the surface of a neuron, seen in conventional microscopy (left) and in super-resolution microscopy (right). Super-resolution makes it possible to reveal the nanometric organization of the receivers. (B) Synaptic nanodomains of NMDA receptors (SR-TESSELER), in control condition (left) and after receptor disorganization using competing peptides. Electrophysiological recordings reveal that the capacity for strengthening synaptic currents (see traces in insets) is very limited after disorganization of nanodomains of NMDA receptors.
© Joana Ferreira / Julien Dupuis / Laurent Groc

- Contact: Laurent Groc
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