GluN3A subunit tunes NMDA receptor synaptic trafficking and content during postnatal brain development
Cell Reports. 2023-05-01; 42(5): 112477
DOI: 10.1016/j.celrep.2023.112477
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González-González IM(1), Gray JA(2), Ferreira J(3), Conde-Dusman MJ(4), Bouchet D(3), Perez-Otaño I(5), Groc L(6).
Author information:
(1)Cellular Neurobiology Laboratory, Centro de Investigación Médica Aplicada
(CIMA) and Universidad de Navarra, Pamplona, Spain; Université de Bordeaux,
CNRS, Interdisciplinary Institute for Neuroscience (IINS), UMR 5297, 33000
Bordeaux, France.
(2)Department of Neurology, Center for Neuroscience, University of California,
Davis, Davis, CA 95618, USA.
(3)Université de Bordeaux, CNRS, Interdisciplinary Institute for Neuroscience
(IINS), UMR 5297, 33000 Bordeaux, France.
(4)Cellular Neurobiology Laboratory, Centro de Investigación Médica Aplicada
(CIMA) and Universidad de Navarra, Pamplona, Spain; Cellular and Systems
Biology, Instituto de Neurociencias, CSIC-UMH, 03550 San Juan de Alicante,
Spain.
(5)Cellular Neurobiology Laboratory, Centro de Investigación Médica Aplicada
(CIMA) and Universidad de Navarra, Pamplona, Spain; Cellular and Systems
Biology, Instituto de Neurociencias, CSIC-UMH, 03550 San Juan de Alicante,
Spain. Electronic address: .
(6)Université de Bordeaux, CNRS, Interdisciplinary Institute for Neuroscience
(IINS), UMR 5297, 33000 Bordeaux, France. Electronic address:
.
Signaling via N-methyl-d-aspartate receptors (NMDARs) is critical for the
maturation of glutamatergic synapses, partly through a developmental switch from
immature synapses expressing primarily GluN2B- and GluN3A-containing subtypes to
GluN2A-rich mature ones. This subunit switch is thought to underlie the synaptic
stabilization of NMDARs necessary for neural network consolidation. However, the
cellular mechanisms controlling the NMDAR exchange remain unclear. Using a
combination of single-molecule and confocal imaging and biochemical and
electrophysiological approaches, we show that surface GluN3A-NMDARs form a
highly diffusive receptor pool that is loosely anchored to synapses. Remarkably,
changes in GluN3A subunit expression selectively alter the surface diffusion and
synaptic anchoring of GluN2A- but not GluN2B-NMDARs, possibly through altered
interactions with cell surface receptors. The effects of GluN3A on NMDAR surface
diffusion are restricted to an early time window of postnatal development in
rodents, allowing GluN3A subunits to control the timing of NMDAR signaling
maturation and neuronal network refinements.
Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.
DOI: 10.1016/j.celrep.2023.112477
PMID: 37149869
Conflict of interest statement: Declaration of interests The authors declare no
competing interests.