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J. Dupuis, L. Ladépêche, L. Groc et al. dans EMBO

Comment la diffusion des récepteurs NMDA contribue à la plasticité synaptique, et comment elle pourrait être altérée dans les encéphalites auto-immunes.

Le 30 avril 2014

Surface dynamics of GluN2B-NMDA receptors controls plasticity of maturing glutamate synapses. Dupuis JP, Ladépêche L, Seth H, Bard L, Varela J, Mikasova L, Bouchet D, Rogemond V, Honnorat J, Hanse E, Groc L. EMBO J. 2014 Mar 3.;

Mechanism elucidated: How lateral diffusion of NMDA receptors contributes to synaptic plasticity, and may be affected in autoimmune encephalitis. 

A research team led by Laurent Groc, a CNRS Research Director at UMR5297 (IINS, Bordeaux), has succeeded in elucidating how the lateral diffusion of NMDA receptors contributes to synaptic long-term potentiation by promoting the accumulation in dendritic spines of the calmodulin-dependent kinase CaMKII. These results just appeared in the EMBO Journal on 16th april 2014. Long term potentiation (LTP), the lasting increase in synaptic transmission following heightened activity, is viewed as the physiological basis of learning.

This plastic remodeling is initiated by bursts of neurotransmission through AMPA receptors which induce a postsynaptic depolarization and the subsequent activation of calcium-permeable NMDA receptors. Calcium influx through these receptors stimulates the accumulation in spines and the activation of calcium- and calmodulin-dependent kinase CamKII, and eventually enhances synaptic strength by recruiting additional AMPA receptors to the synapse. It was recently shown in immature neurons that these adaptations are paralleled by a quick switch in the composition of synaptic NMDA receptors, which rapidly change from GluN2B- towards GluN2A-predominant receptors (Bellone and Nicoll, 2007).

However, the cellular mechanisms responsible for this switch and for the recruitment of CamKII to spines remained poorly understood. What we show here using a combination of single nanoparticle tracking and electrophysiology is that this rearrangement relies on a dynamic surface redistribution of GluN2B-NMDAR. Through their direct interaction, this increase in the lateral diffusion of surface GluN2B-NMDAR favors the intracellular redistribution of CaMKII towards dendritic spines where it initiates functional and morphological adaptations.

We also show that antibodies against NMDA receptors from patients with autoimmune encephalitis prevent this redistribution and consequently impair LTP, which could provide an explanation for the cognitive deficits associated with this disease. In conclusion, we uncover a non-canonical mechanism by which the surface dynamics of GluN2B-NMDAR plays a critical role in synaptic plasticity through a direct interplay with CaMKII.

Abstract PubMed

Julien Dupuis (julien.dupuis @
Dernière mise à jour le 30.04.2014

1ers auteurs

Julien Dupuis

Present: Postdoc, IINS (Bordeaux), Team Development and Adaptation of Neuronal Circuits (Laurent Groc)
2010-2012: Postdoc, IMN (Bordeaux), Team Synaptic and Cellular Dynamics of Neuronal Networks (Jérôme Baufreton)
2008-2010: Postdoc, CRCA (Toulouse), Team Perception, Learning and Memory in Insects (Martin Giurfa)
2005-2008: PhD, IBS (CEA Grenoble), Team Channels (Michel Vivaudou)


Laurent Ladépêche
Present: Postdoc, ICFO (Barcelona), Team Advanced Fluroescence Imaging and Biophysics (Melike Lakadamyali)
2012-2013: Postdoc, IINS (Bordeaux), Team Development and Adaptation of Neuronal Circuits (Laurent Groc)
2009-2012: PhD, IINS (Bordeaux), Team Development and Adaptation of Neuronal Circuits (Laurent Groc)