title: Surface dynamics of GluN2B-NMDA receptors controls plasticity of maturing glutamate synapses.
abstract: NMDA-type glutamate receptors (NMDAR) are central actors in the plasticity of excitatory synapses. During adaptive processes, the number and composition of synaptic NMDAR can be rapidly modified, as in neonatal hippocampal synapses where a switch from predominant GluN2B- to GluN2A-containing receptors is observed after the induction of long-term potentiation (LTP). However, the cellular pathways by which surface NMDAR subtypes are dynamically regulated during activity-dependent synaptic adaptations remain poorly understood. Using a combination of high-resolution single nanoparticle imaging and electrophysiology, we show here that GluN2B-NMDAR are dynamically redistributed away from glutamate synapses through increased lateral diffusion during LTP in immature neurons. Strikingly, preventing this activity-dependent GluN2B-NMDAR surface redistribution through cross-linking, either with commercial or with autoimmune anti-NMDA antibodies from patient with neuropsychiatric symptoms, affects the dynamics and spine accumulation of CaMKII and impairs LTP. Interestingly, the same impairments are observed when expressing a mutant of GluN2B-NMDAR unable to bind CaMKII. We thus uncover a non-canonical mechanism by which GluN2B-NMDAR surface dynamics plays a critical role in the plasticity of maturing synapses through a direct interplay with CaMKII.
authors.affiliation: Interdisciplinary Institute for Neuroscience University de Bordeaux UMR 5297, Bordeaux, France.
authors.forename: Julien P
authors.initials: JP
authors.lastname: Dupuis
authors.forename: Laurent
authors.initials: L
authors.lastname: Ladépêche
authors.forename: Henrik
authors.initials: H
authors.lastname: Seth
authors.forename: Lucie
authors.initials: L
authors.lastname: Bard
authors.forename: Juan
authors.initials: J
authors.lastname: Varela
authors.forename: Lenka
authors.initials: L
authors.lastname: Mikasova
authors.forename: Delphine
authors.initials: D
authors.lastname: Bouchet
authors.forename: Véronique
authors.initials: V
authors.lastname: Rogemond
authors.forename: Jérôme
authors.initials: J
authors.lastname: Honnorat
authors.forename: Eric
authors.initials: E
authors.lastname: Hanse
authors.forename: Laurent
authors.initials: L
authors.lastname: Groc
mesh_terms: D000818:Animals; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism; D008954:Models, Biological; D009473:Neuronal Plasticity; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D013569:Synapses / Q000502:physiology*
chemical_list: C121001:NR2B NMDA receptor; D016194:Receptors, N-Methyl-D-Aspartate; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2