Differential Nanoscale Topography and Functional Role of GluN2-NMDA Receptor Subtypes at Glutamatergic Synapses
Neuron. 2018-10-01; 100(1): 106-119.e7
DOI: 10.1016/j.neuron.2018.09.012
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1. Neuron. 2018 Oct 10;100(1):106-119.e7. doi: 10.1016/j.neuron.2018.09.012. Epub
2018 Sep 27.
Differential Nanoscale Topography and Functional Role of GluN2-NMDA Receptor
Subtypes at Glutamatergic Synapses.
Kellermayer B(1), Ferreira JS(2), Dupuis J(2), Levet F(3), Grillo-Bosch D(2),
Bard L(4), Linarès-Loyez J(5), Bouchet D(2), Choquet D(3), Rusakov DA(6), Bon
P(5), Sibarita JB(2), Cognet L(5), Sainlos M(2), Carvalho AL(7), Groc L(8).
Author information:
(1)Université de Bordeaux, Interdisciplinary Institute for Neuroscience, UMR
5297, 33000 Bordeaux, France; CNRS, IINS UMR 5297, Bordeaux, France; CNC-Center
for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra,
Portugal. Electronic address: .
(2)Université de Bordeaux, Interdisciplinary Institute for Neuroscience, UMR
5297, 33000 Bordeaux, France; CNRS, IINS UMR 5297, Bordeaux, France.
(3)Université de Bordeaux, Interdisciplinary Institute for Neuroscience, UMR
5297, 33000 Bordeaux, France; CNRS, IINS UMR 5297, Bordeaux, France; CNRS,
Bordeaux Imaging Center UMS 3420, 33000 Bordeaux, France.
(4)Université de Bordeaux, Interdisciplinary Institute for Neuroscience, UMR
5297, 33000 Bordeaux, France; CNRS, IINS UMR 5297, Bordeaux, France; UCL
Institute of Neurology, University College London, London, UK.
(5)Institut d’Optique & CNRS, LP2N UMR 5298, 33400 Talence, France; Université de
Bordeaux, Laboratoire Photonique Numérique et Nanosciences, UMR 5298, 33400
Talence, France.
(6)UCL Institute of Neurology, University College London, London, UK.
(7)CNC-Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504
Coimbra, Portugal; Department of Life Sciences, Faculty of Sciences and
Technology, University of Coimbra, 3004-517 Coimbra, Portugal.
(8)Université de Bordeaux, Interdisciplinary Institute for Neuroscience, UMR
5297, 33000 Bordeaux, France; CNRS, IINS UMR 5297, Bordeaux, France. Electronic
address: .
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.
Copyright © 2018 Elsevier Inc. All rights reserved.
DOI: 10.1016/j.neuron.2018.09.012
PMID: 30269991