Surface dynamics of GluN2B-NMDA receptors controls plasticity of maturing glutamate synapses

Julien P Dupuis, Laurent Ladépêche, Henrik Seth, Lucie Bard, Juan Varela, Lenka Mikasova, Delphine Bouchet, Véronique Rogemond, Jérôme Honnorat, Eric Hanse, Laurent Groc

Research output: Contribution to journalArticlepeer-review

94 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)842-861
Number of pages20
JournalEMBO Journal
Volume33
Issue number8
Early online date3 Mar 2014
DOIs
Publication statusPublished - 16 Apr 2014

Keywords

  • Development
  • High-resolution imaging
  • Lateral diffusion
  • Long-term potentiation
  • Synaptic plasticity

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