Cited by 233Neuroscience and Neuropharmacology ResearchAdvanced Fluorescence Microscopy TechniquesGenetics and Neurodevelopmental Disorders

Synaptic nanomodules underlie the organization and plasticity of spine synapses

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Hruska, Martin, Henderson, Nathan, Le Marchand, Sylvain J., Jafri, Haani, Dalva, Matthew B.·2018·Nature Neuroscience

Abstract

Experience results in long-lasting changes in dendritic spine size, yet how the molecular architecture of the synapse responds to plasticity remains poorly understood. Here a combined approach of multicolor stimulated emission depletion microscopy (STED) and confocal imaging in rat and mouse demonstrates that structural plasticity is linked to the addition of unitary synaptic nanomodules to spines. Spine synapses in vivo and in vitro contain discrete and aligned subdiffraction modules of pre- and postsynaptic proteins whose number scales linearly with spine size. Live-cell time-lapse super-resolution imaging reveals that NMDA receptor-dependent increases in spine size are accompanied both by enhanced mobility of pre- and postsynaptic modules that remain aligned with each other and by a coordinated increase in the number of nanomodules. These findings suggest a simplified model for experience-dependent structural plasticity relying on an unexpectedly modular nanomolecular architecture of synaptic proteins.

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  • 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 [256]

    The Results section on spine size reports discrete clusters of PSD-95 and presynaptic proteins, not AMPARs. The Discussion mentions AMPARs only as possible proteins involved in forming new nanomodules; it does not describe AMPAR clusters or their distribution around the PSD. Searches for AMPAR clustering and localization found no passage establishing the claim. (LLM, conf=0.73)

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References 59 · Cited by 233

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Authors
Hruska, M., Henderson, N., Le Marchand, S. J., Jafri, H., & Dalva, M. B.
Affiliations
Thomas Jefferson University (US)
Corresponding author
Dalva, Matthew B.
Venue
Nature Neuroscience
Published
2018-04-23
Volume
21
Issue
5
Pages
671-682
ISSN
  • 1097-6256 (ISSN-L)
  • 1546-1726
OpenAlex
W2802771436
Cited by
233
References
59
Citations by year
2026: 18 · 2025: 19 · 2024: 22 · 2023: 20 · 2022: 30 · 2021: 42 · 2020: 39 · 2019: 29 · 2018: 14
FWCI
14.12
Type
journal article
Language
en
Open access
Locations
  • Nature Neuroscience (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • The Medicine Forum (submittedVersion)
Funders
  • National Institute of Mental Health (R01MH100093)
  • National Institute on Drug Abuse (R01DA022727)
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 › Genetics › Genetics and Neurodevelopmental Disorders
Keywords
dendritic spines, synaptic plasticity, structural plasticity, NMDA receptor, experience-dependent plasticity, super-resolution imaging, STED microscopy, time-lapse imaging
MeSH terms
Disks Large Homolog 4 Protein, Animals, Immunohistochemistry, Models, Neurological, Neuronal Plasticity, Plasmids, Synapses, Synaptic Vesicles, Receptors, Presynaptic, Long-Term Potentiation, Dendritic Spines, Mice, Rats, Primary Cell Culture

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