L\u2019adaptation des synapses excitatrices est une des bases de la plasticit\u00e9 c\u00e9r\u00e9brale, et implique le recrutement de r\u00e9cepteurs du glutamate de type NMDA. Des chercheurs de l\u2019IINS (UMR 5297), du LP2N (Institut d\u2019Optique), du University College London (UK), et de l\u2019Universit\u00e9 de Coimbra (Portugal) ont caract\u00e9ris\u00e9 l\u2019organisation nanom\u00e9trique de ces r\u00e9cepteurs aux synapses, et comment celle-ci influence leur adaptation. Publi\u00e9s dans la revue Neuron, ces travaux apportent un \u00e9clairage nouveau sur les m\u00e9canismes \u00e0 l\u2019\u0153uvre pendant l\u2019apprentissage et la m\u00e9morisation.<\/p>\n
En effet, les synapses glutamatergiques supportent l\u2019essentiel des neurotransmissions excitatrices dans le cerveau et ont la capacit\u00e9 de s’adapter, un processus de plasticit\u00e9 g\u00e9n\u00e9ralement consid\u00e9r\u00e9 comme une des bases de l\u2019apprentissage et de la m\u00e9moire. Les r\u00e9cepteurs du glutamate de type NMDA (NMDAR) sont des acteurs cl\u00e9s de ces changements d\u2019efficacit\u00e9, et ont par cons\u00e9quent \u00e9t\u00e9 intensivement \u00e9tudi\u00e9s au cours des derni\u00e8res d\u00e9cennies par manipulations g\u00e9n\u00e9tiques ou pharmacologiques. Deux sous-types principaux de NMDAR, ceux contenant la sous-unit\u00e9 GluN2A ou GluN2B, influent directement sur la capacit\u00e9 de renforcement ou d\u2019affaiblissement des synapses. De v\u00e9ritables r\u00e9gulateurs de l\u2019adaptabilit\u00e9 des synapses excitatrices!<\/p>\n
N\u00e9anmoins, nous n\u2019avions jusqu\u2019alors aucune vision de comment ces GluN2A- et GluN2B-NMDAR sont organis\u00e9s au sein des synapses, de l\u2019\u00e9volution de cette organisation au cours du d\u00e9veloppement, ni de comment cette organisation peut participer \u00e0 la plasticit\u00e9 synaptique. En combinant des approches de microscopie de super-r\u00e9solution et de d\u2019\u00e9lectrophysiologie dans l\u2019hippocampe, nous avons observ\u00e9 que les deux types de r\u00e9cepteurs sont organis\u00e9s en nano-domaines distincts qui varient en nombre, surface, morphologie et localisation au cours du d\u00e9veloppement. Ces nano-domaines r\u00e9pondent \u00e0 des m\u00e9canismes de r\u00e9gulation sp\u00e9cifiques \u00e0 chaque sous-type de r\u00e9cepteurs impliquant des interactions avec des prot\u00e9ines d\u2019\u00e9chafaudage. Pour comprendre comment cette distribution nanom\u00e9trique pouvait influer sur la signalisation synaptique, ils ont ensuite s\u00e9lectivement d\u00e9sorganis\u00e9 ces nano-domaines et, de mani\u00e8re inattendue, cela entrainait des changements bidirectionnels de la capacit\u00e9 d\u2019adaptation des synapses! Ces d\u00e9couvertes r\u00e9v\u00e8lent pour la premi\u00e8re fois que l\u2019organisation nanom\u00e9trique des r\u00e9cepteurs joue un r\u00f4le cl\u00e9 dans la plasticit\u00e9 des synapses. Elles apportent un \u00e9clairage nouveau sur notre compr\u00e9hension des m\u00e9canismes mol\u00e9culaires \u00e0 l\u2019\u0153uvre lors des processus d\u2019apprentissage et de m\u00e9morisation.<\/p>\n
<\/p>\n
Nanoscopic change, macroscopic effect\u00a0: when the NMDA receptor tunes the synaptic plasticity\u00a0!<\/strong><\/p>\n <\/p>\n Glutamatergic synapses mediate most of excitatory neurotransmissions in the brain and have the ability to adapt their strength in response to salient environmental stimuli, a neuronal plasticity process that has been proposed to support learning and memory formation. NMDA glutamate receptors (NMDAR) were found to be central actors of these experience-dependent changes in transmission efficacy. Thus, they have been extensively studied over the past decades through genetic and pharmacological manipulations. These studies have revealed that two main subtypes of NMDAR can be found in the forebrain: those containing the GluN2A and those containing the GluN2B subunit, which display specific biophysical, pharmacological and signaling properties. An interesting feature of these two predominant subtypes is that their respective abundance at synapses changes along brain development or sensory experience, and directly influences the ability of synapses to strengthen or weaken.<\/p>\n However, how the spatial distribution of GluN2A- and GluN2B-NMDAR at synapses evolves during maturation or activity-elicited modifications, and how it may affect synaptic signaling and adaptation remained open questions. In a joint effort between researchers of IINS (University of Bordeaux\/CNRS UMR 5297), LP2N (University of Bordeaux\/Institut d\u2019Optique), University College London (UK), and of the University of Coimbra (Portugal), we used super-resolution microscopy and electrophysiological recordings in hippocampal neurons to investigate the nanoscale organization of GluN2A- and GluN2B-NMDAR at synapses and how it influences their adaptation. Both receptor subtypes were found to be organized in separate nanodomains which varied in number, area, shape, and localization over the course of development. These nanodomains displayed regulation mechanisms that were specific to each receptor subtype and involved interactions with scaffolding proteins of the postsynaptic density. To explore how this finely controlled distribution may influence synaptic signaling, we then selectively disrupted the organization of either GluN2A- or GluN2B-NMDAR nanodomains. To our surprise, acting on one or the other allowed to bi-directionally influence the adaptation of synapses: while disorganizing GluN2A-NMDAR nanodomains enhanced the strengthening of neuronal connections, disrupting the organization of GluN2B-NMDAR resulted in the exact opposite! These investigations reveal for the first time that the nanoscale organization of receptors plays a key role in NMDAR signaling at synapses, and likely influences the plasticity of neuronal networks.<\/p>\n Pour en savoir plus<\/strong><\/p>\n Kellermayer B*, Ferreira JS*, Dupuis J*, Levet F\u00a7, Grillo-Bosch D\u00a7, Bard L\u00a7, Linar\u00e8s-Loyez J, Bouchet D, Choquet D, Rusakov DA, Bon P, Sibarita JB, Cognet L, Sainlos M, Carvalho AL, Groc LDifferential Nanoscale Topography and Functional Role of GluN2-NMDA Receptor Subtypes at Glutamatergic Synapses – Published: September 27, 2018 \u00b7 DOI: https:\/\/doi.org\/10.1016\/j.neuron.2018.09.012<\/p>\n Contact chercheur<\/strong><\/p>\n Laurent Groc<\/p>\n Institut Interdisciplinaire de Neurosciences<\/p>\n UMR5297 (CNRS\/Universit\u00e9 de Bordeaux)<\/p>\n 146 rue L\u00e9o Saignat<\/p>\n CS 61292 Case 130<\/p>\n 33076 Bordeaux Cedex<\/p>\n Tel: 05 33 51 47 62<\/p>\n laurent.groc@u-bordeaux.fr<\/p>\n","protected":false},"excerpt":{"rendered":" L\u2019adaptation des synapses excitatrices est une des bases de la plasticit\u00e9 c\u00e9r\u00e9brale, et implique le recrutement de r\u00e9cepteurs du glutamate de type NMDA. Des chercheurs de l\u2019IINS (UMR 5297), du LP2N (Institut d\u2019Optique), du University College London (UK), et de l\u2019Universit\u00e9 de Coimbra (Portugal) ont caract\u00e9ris\u00e9 l\u2019organisation nanom\u00e9trique de ces r\u00e9cepteurs aux synapses, et comment […]<\/p>\n","protected":false},"author":4,"featured_media":10011,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[25],"tags":[31],"class_list":["post-9999","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-uncategorized","tag-actualite-en"],"publishpress_future_action":{"enabled":false,"date":"2026-04-24 12:16:07","action":"change-status","newStatus":"draft","terms":[],"taxonomy":"category"},"publishpress_future_workflow_manual_trigger":{"enabledWorkflows":[]},"_links":{"self":[{"href":"https:\/\/www.neurosciences.asso.fr\/en\/wp-json\/wp\/v2\/posts\/9999","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.neurosciences.asso.fr\/en\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.neurosciences.asso.fr\/en\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.neurosciences.asso.fr\/en\/wp-json\/wp\/v2\/users\/4"}],"replies":[{"embeddable":true,"href":"https:\/\/www.neurosciences.asso.fr\/en\/wp-json\/wp\/v2\/comments?post=9999"}],"version-history":[{"count":1,"href":"https:\/\/www.neurosciences.asso.fr\/en\/wp-json\/wp\/v2\/posts\/9999\/revisions"}],"predecessor-version":[{"id":10001,"href":"https:\/\/www.neurosciences.asso.fr\/en\/wp-json\/wp\/v2\/posts\/9999\/revisions\/10001"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.neurosciences.asso.fr\/en\/wp-json\/wp\/v2\/media\/10011"}],"wp:attachment":[{"href":"https:\/\/www.neurosciences.asso.fr\/en\/wp-json\/wp\/v2\/media?parent=9999"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.neurosciences.asso.fr\/en\/wp-json\/wp\/v2\/categories?post=9999"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.neurosciences.asso.fr\/en\/wp-json\/wp\/v2\/tags?post=9999"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}