GluN3A subunit tunes NMDA receptor synaptic trafficking and content during postnatal brain development
Summary: 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...
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Format: | Article |
Language: | English |
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Elsevier
2023-05-01
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Series: | Cell Reports |
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Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124723004886 |
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author | Inmaculada M. González-González John A. Gray Joana Ferreira María Jose Conde-Dusman Delphine Bouchet Isabel Perez-Otaño Laurent Groc |
author_facet | Inmaculada M. González-González John A. Gray Joana Ferreira María Jose Conde-Dusman Delphine Bouchet Isabel Perez-Otaño Laurent Groc |
author_sort | Inmaculada M. González-González |
collection | DOAJ |
description | Summary: 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. |
first_indexed | 2024-04-09T13:57:08Z |
format | Article |
id | doaj.art-bf9666f4a96d4c7eb23dd56fc77bb8ac |
institution | Directory Open Access Journal |
issn | 2211-1247 |
language | English |
last_indexed | 2024-04-09T13:57:08Z |
publishDate | 2023-05-01 |
publisher | Elsevier |
record_format | Article |
series | Cell Reports |
spelling | doaj.art-bf9666f4a96d4c7eb23dd56fc77bb8ac2023-05-08T04:09:18ZengElsevierCell Reports2211-12472023-05-01425112477GluN3A subunit tunes NMDA receptor synaptic trafficking and content during postnatal brain developmentInmaculada M. González-González0John A. Gray1Joana Ferreira2María Jose Conde-Dusman3Delphine Bouchet4Isabel Perez-Otaño5Laurent Groc6Cellular 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, FranceDepartment of Neurology, Center for Neuroscience, University of California, Davis, Davis, CA 95618, USAUniversité de Bordeaux, CNRS, Interdisciplinary Institute for Neuroscience (IINS), UMR 5297, 33000 Bordeaux, FranceCellular 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, SpainUniversité de Bordeaux, CNRS, Interdisciplinary Institute for Neuroscience (IINS), UMR 5297, 33000 Bordeaux, FranceCellular 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; Corresponding authorUniversité de Bordeaux, CNRS, Interdisciplinary Institute for Neuroscience (IINS), UMR 5297, 33000 Bordeaux, France; Corresponding authorSummary: 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.http://www.sciencedirect.com/science/article/pii/S2211124723004886glutamate receptordiffusionhippocampusmaturationglycine |
spellingShingle | Inmaculada M. González-González John A. Gray Joana Ferreira María Jose Conde-Dusman Delphine Bouchet Isabel Perez-Otaño Laurent Groc GluN3A subunit tunes NMDA receptor synaptic trafficking and content during postnatal brain development Cell Reports glutamate receptor diffusion hippocampus maturation glycine |
title | GluN3A subunit tunes NMDA receptor synaptic trafficking and content during postnatal brain development |
title_full | GluN3A subunit tunes NMDA receptor synaptic trafficking and content during postnatal brain development |
title_fullStr | GluN3A subunit tunes NMDA receptor synaptic trafficking and content during postnatal brain development |
title_full_unstemmed | GluN3A subunit tunes NMDA receptor synaptic trafficking and content during postnatal brain development |
title_short | GluN3A subunit tunes NMDA receptor synaptic trafficking and content during postnatal brain development |
title_sort | glun3a subunit tunes nmda receptor synaptic trafficking and content during postnatal brain development |
topic | glutamate receptor diffusion hippocampus maturation glycine |
url | http://www.sciencedirect.com/science/article/pii/S2211124723004886 |
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