Surface dynamics of GluN2B-NMDA receptors controls plasticity of maturing glutamate synapses
The EMBO Journal. 2014-03-03; 33(8): 842-861
Read on PubMed
EMBO J. 2014 Apr 16;33(8):781-2.
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.