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Cited by 324Neuroscience and Neuropharmacology ResearchMemory and Neural MechanismsNicotinic Acetylcholine Receptors Study

Hippocampal LTP and contextual learning require surface diffusion of AMPA receptors

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Penn, A. C., Zhang, C. L., Georges, F., Royer, L., Breillat, C., Hosy, E., Petersen, J. D., Humeau, Y. +1 more·2017·Nature
DOI 10.1038/nature23658PMC PMC5683353
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Abstract

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.

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  • Interfering with the surface diffusion of AMPARs by receptor cross-linking markedly impairs LTP.

    “Consistent with this result is the finding that interfering with the surface diffusion of AMPARs by receptor cross-linking markedly impairs LTP (345–347).”

    From Synaptic memory and CaMKII (2023) · cites this paper as [345]

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References 33 · Cited by 324

Research works printed but not linked: 30

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Authors
Penn, A. C., Zhang, C. L., Georges, F., Royer, L., Breillat, C., Hosy, E., Petersen, J. D., Humeau, Y., & Choquet, D.
Affiliations
Centre National de la Recherche Scientifique (FR)
Corresponding author
Choquet, D.
ORCID
Venue
Nature
Publisher
Springer Science and Business Media LLC
Published
2017-09
Volume
549
Issue
7672
Pages
384-388
ISSN
  • 0028-0836 (ISSN-L)
  • 1476-4687
DOI
10.1038/nature23658
PMC
PMC5683353
OpenAlex
W2735674872
Cited by
324
References
33
Citations by year
2026: 13 · 2025: 24 · 2024: 31 · 2023: 31 · 2022: 48 · 2021: 57 · 2020: 41 · 2019: 37 · 2018: 37 · 2017: 5
FWCI
16.07
Type
journal article
Language
en
Open access
Licence
www.springer.com/tdm (tdm)
Locations
  • Nature (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • Sussex Research Online (University of Sussex) (submittedVersion)
  • HAL (submittedVersion)
  • HAL (submittedVersion, other-oa)
  • RePEc: Research Papers in Economics (submittedVersion)
  • Figshare (submittedVersion)
Funders
  • Agence Nationale de la Recherche (ANR-10-INBS-0004)
  • Medical Research Council (MR/M020746/1)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
Keywords
diffusion, AMPA receptor trafficking, long-term potentiation, contextual learning, fear conditioning, hippocampus, synaptic plasticity, Schaffer collaterals, CA1, glutamate receptors, memory formation, dorsal hippocampus, excitatory synaptic transmission, glutamate release, postsynaptic receptors
MeSH terms
Animals, Avidin, Biotin, Cell Membrane, Conditioning, Classical, Cross-Linking Reagents, Diffusion, Fear, Female, Hippocampus, Immunoglobulin G, Male, Mice, Inbred C57BL, Synaptic Transmission, Synapses, Long-Term Potentiation, Receptors, AMPA, Excitatory Postsynaptic Potentials, Mice, Rats

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