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Cited by 617Neuroscience and Neuropharmacology ResearchAdvanced Fluorescence Microscopy TechniquesReceptor Mechanisms and Signaling

Super-Resolution Imaging Reveals That AMPA Receptors Inside Synapses Are Dynamically Organized in Nanodomains Regulated by PSD95

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Nair, D., Hosy, E., Petersen, J. D., Constals, A., Giannone, G., Choquet, D., Sibarita, J.-B.·2013·Journal of Neuroscience
DOI 10.1523/jneurosci.2381-12.2013PMC PMC6619720
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Abstract

The spatiotemporal organization of neurotransmitter receptors in postsynaptic membranes is a fundamental determinant of synaptic transmission and information processing by the brain. Using four independent super-resolution light imaging methods and EM of genetically tagged and endogenous receptors, we show that, in rat hippocampal neurons, AMPARs are often highly concentrated inside synapses into a few clusters of ∼70 nm that contain ∼20 receptors. AMPARs are stabilized reversibly in these nanodomains and diffuse freely outside them. Nanodomains are dynamic in their shape and position within synapses and can form or disappear within minutes, although they are mostly stable for up to 1 h. AMPAR nanodomains are often, but not systematically, colocalized with clusters of the scaffold protein PSD95, which are generally of larger size than AMPAR nanoclusters. PSD95 expression level regulates AMPAR nanodomain size and compactness in parallel to miniature EPSC amplitude. Monte Carlo simulations further indicate the impact of AMPAR concentration in clusters on the efficacy of synaptic transmission. The observation that AMPARs are highly concentrated in nanodomains, instead of diffusively distributed in the PSD as generally thought, has important consequences on our understanding of excitatory neurotransmission. Furthermore, our results indicate that glutamatergic synaptic transmission is controlled by the nanometer-scale regulation of the size of these highly concentrated nanodomains.

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Crossref · 10.1523/jneurosci.2381-12.2013

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  • Presynaptic RIM nanoclusters closely align with concentrated postsynaptic receptors and scaffolding proteins.

    “These presynaptic RIM nanoclusters closely aligned with concentrated postsynaptic receptors and scaffolding proteins4–6, suggesting a transsynaptic molecular “nanocolumn.””

    From A trans-synaptic nanocolumn aligns neurotransmitter release to receptors (2016) · cites this paper as [5]

    The Abstract reports concentrated postsynaptic AMPA-receptor nanodomains that are often, but not always, colocalized with PSD95 scaffold clusters. The Discussion only proposes a possible correlation with presynaptic release sites; it does not establish that presynaptic RIM nanoclusters closely align with those postsynaptic clusters. No page numbers are available in our copy. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • The alignment of pre- and postsynaptic nanoscale subdomains suggests that even small synapses may be composed of dynamic functional modules.

    “The alignment of pre and postsynaptic nanoscale subdomains4–6 suggests that even small synapses may be composed of dynamic functional modules28,29.”

    From A trans-synaptic nanocolumn aligns neurotransmitter release to receptors (2016) · cites this paper as [5]

    The Discussion (page unavailable) describes dynamic AMPAR nanodomains that may act as functional units activated by single-vesicle release, supporting the proposed module concept. The cited paper does not specifically establish that this organization occurs in small synapses; the sentence’s alignment claim is attached to other citations. (LLM, conf=0.78)

    Experimental — accuracy not yet measured

  • The average estimated diameter of RIM1/2 nanoclusters is very close to the reported size of PSD-95 and AMPA receptor nanoclusters.

    “The average estimated diameter of ~80 nm for RIM1/2 NCs was very close to the reported size of PSD-95 and AMPA receptor (AMPAR) NCs4–6.”

    From A trans-synaptic nanocolumn aligns neurotransmitter release to receptors (2016) · cites this paper as [5]

    The ‘Subsynaptic AMPAR clusters’ section reports AMPAR nanodomain axes near 80 nm, supporting that comparison. But ‘Nanoscale co-organization of PSD95 and AMPARs’ (Fig. 7E) reports PSD95 subdomain axes of 158.2 and 102.2 nm and explicitly describes the AMPAR nanodomains as smaller. The copy does not support treating both reported sizes as very close to 80 nm. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

  • Glutamate receptors localize to submicron scale clusters within the synaptic membrane.

    “In addition, recent studies have shown that glutamate receptors localize to submicron scale clusters within the synaptic membrane as shown by various techniques ranging from EM to PALM microscopy (Ehlers et al., 2007; MacGillavry et al., 2013; Nair et al., 2013).”

    From Barriers in the brain: resolving dendritic spine morphology and compartmentalization (2014) · cites this paper as Nair et al., 2013

  • AMPARs form discrete clusters scattered around the PSD.

    “AMPARs form discrete clusters scattered around the PSD (256–259).”

    From Synaptic memory and CaMKII (2023) · cites this paper as [257]

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Cites

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Cited by

Sorted by citations

Authors
Nair, D., Hosy, E., Petersen, J. D., Constals, A., Giannone, G., Choquet, D., & Sibarita, J.-B.
Affiliations
Centre National de la Recherche Scientifique (FR)
ORCID
Venue
Journal of Neuroscience
Publisher
Society for Neuroscience
Published
2013-08-07
Volume
33
Issue
32
Pages
13204-13224
ISSN
  • 0270-6474 (ISSN-L)
  • 1529-2401
DOI
10.1523/jneurosci.2381-12.2013
PMC
PMC6619720
OpenAlex
W2167612537
Cited by
617
References
6
Citations by year
2026: 33 · 2025: 42 · 2024: 55 · 2023: 43 · 2022: 59 · 2021: 65 · 2020: 57 · 2019: 47 · 2018: 54 · 2017: 46 · 2016: 43 · 2015: 30 · 2014: 34 · 2013: 8 · 2012: 1
FWCI
18.81
Type
journal article
Language
en
Open access
Locations
  • Journal of Neuroscience (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • University of Pennsylvania
  • European Commission
  • Centre National de la Recherche Scientifique
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biophysics › Advanced Fluorescence Microscopy Techniques
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
Keywords
AMPA receptors, PSD-95, receptor clustering, postsynaptic density, excitatory synaptic transmission, miniature EPSCs, hippocampal neurons, glutamatergic synapses, receptor diffusion, synaptic scaffolds
MeSH terms
Homer Scaffolding Proteins, Disks Large Homolog 4 Protein, Action Potentials, Animals, Carrier Proteins, Cells, Cultured, Embryo, Mammalian, Female, Hippocampus, Male, Membrane Proteins, Models, Biological, Mutation, Neurons, Picrotoxin, Stochastic Processes, Synapses, Synaptic Membranes, Calcium Channels, Receptors, AMPA, GABA Antagonists, Excitatory Postsynaptic Potentials, Protein Transport, Intracellular Signaling Peptides and Proteins, Nanostructures, Green Fluorescent Proteins, Rats

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