Hippocampal LTP and contextual learning require surface diffusion of AMPA receptors.

A. C. Penn, C. L. Zhang, F. Georges, L. Royer, C. Breillat, E. Hosy, J. D. Petersen, Y. Humeau, D. Choquet
Nature. 2017-09-13; 549(7672): 384-388
DOI: 10.1038/nature23658

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1. Nature. 2017 Sep 21;549(7672):384-388. doi: 10.1038/nature23658. Epub 2017 Sep

Hippocampal LTP and contextual learning require surface diffusion of AMPA

Penn AC(1)(2)(3), Zhang CL(1)(2), Georges F(1)(2)(4), Royer L(1)(2), Breillat
C(1)(2), Hosy E(1)(2), Petersen JD(1)(2)(5), Humeau Y(1)(2), Choquet D(1)(2)(5).

Author information:
(1)University of Bordeaux, Interdisciplinary Institute for Neuroscience, UMR5297,
F-33000 Bordeaux, France.
(2)CNRS, Interdisciplinary Institute for Neuroscience, UMR 5297, F-33000
Bordeaux, France.
(3)Sussex Neuroscience, School of Life Sciences, University of Sussex, Brighton
BN1 9QG, UK.
(4)University of Bordeaux, Institute of Neurodegenerative Diseases, CNRS UMR
5293, 146 Rue Léo Saignat, 33076 Bordeaux, France.
(5)Bordeaux Imaging Center, UMS 3420 CNRS, US4 INSERM, University of Bordeaux,
Bordeaux, France.

Comment in
Nat Rev Neurosci. 2017 Nov;18(11):642.

Long-term potentiation (LTP) of excitatory synaptic transmission has long been
considered a cellular correlate for learning and memory. Early LTP (less than
1 h) had initially been explained either by presynaptic increases in glutamate
release or by direct modification of postsynaptic AMPA
(α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) receptor function.
Compelling models have more recently proposed that synaptic potentiation can
occur by the recruitment of additional postsynaptic AMPA receptors (AMPARs),
sourced either from an intracellular reserve pool by exocytosis or from nearby
extra-synaptic receptors pre-existing on the neuronal surface. However, the exact
mechanism through which synapses can rapidly recruit new AMPARs during early LTP
remains unknown. In particular, direct evidence for a pivotal role of AMPAR
surface diffusion as a trafficking mechanism in synaptic plasticity is still
lacking. Here, using AMPAR immobilization approaches, we show that interfering
with AMPAR surface diffusion markedly impairs synaptic potentiation of Schaffer
collaterals and commissural inputs to the CA1 area of the mouse hippocampus in
cultured slices, acute slices and in vivo. Our data also identify distinct
contributions of various AMPAR trafficking routes to the temporal profile of
synaptic potentiation. In addition, AMPAR immobilization in vivo in the dorsal
hippocampus inhibited fear conditioning, indicating that AMPAR diffusion is
important for the early phase of contextual learning. Therefore, our results
provide a direct demonstration that the recruitment of new receptors to synapses
by surface diffusion is a critical mechanism for the expression of LTP and
hippocampal learning. Since AMPAR surface diffusion is dictated by weak Brownian
forces that are readily perturbed by protein-protein interactions, we anticipate
that this fundamental trafficking mechanism will be a key target for modulating
synaptic potentiation and learning.

DOI: 10.1038/nature23658
PMCID: PMC5683353
PMID: 28902836 [Indexed for MEDLINE]

Auteurs Bordeaux Neurocampus