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Cited by 183Neuroscience and Neuropharmacology ResearchCellular transport and secretionGenetics and Neurodevelopmental Disorders

Pre-post synaptic alignment through neuroligin-1 tunes synaptic transmission efficiency

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Haas, Kalina T, Compans, Benjamin, Letellier, Mathieu, Bartol, Thomas M, Grillo-Bosch, Dolors, Sejnowski, Terrence J, Sainlos, Matthieu, Choquet, Daniel +2 more·2018·eLife
DOI 10.7554/elife.31755PMC PMC6070337

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Abstract

The nanoscale organization of neurotransmitter receptors regarding pre-synaptic release sites is a fundamental determinant of the synaptic transmission amplitude and reliability. How modifications in the pre- and post-synaptic machinery alignments affects synaptic currents, has only been addressed with computer modelling. Using single molecule super-resolution microscopy, we found a strong spatial correlation between AMPA receptor (AMPAR) nanodomains and the post-synaptic adhesion protein neuroligin-1 (NLG1). Expression of a truncated form of NLG1 disrupted this correlation without affecting the intrinsic AMPAR organization, shifting the pre-synaptic release machinery away from AMPAR nanodomains. Electrophysiology in dissociated and organotypic hippocampal rodent cultures shows these treatments significantly decrease AMPAR-mediated miniature and EPSC amplitudes. Computer modelling predicts that ~100 nm lateral shift between AMPAR nanoclusters and glutamate release sites induces a significant reduction in AMPAR-mediated currents. Thus, our results suggest the synapses necessity to release glutamate precisely in front of AMPAR nanodomains, to maintain a high synaptic responses efficiency.

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  • AMPAR clusters are juxtaposed across from the presynaptic release site.

    “Of particular interest is the finding that these clusters are juxtaposed across from presynaptic release site (251, 252, 260).”

    From Synaptic memory and CaMKII (2023) · cites this paper as [260]

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References 59 · Cited by 183

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Authors
Haas, K. T., Compans, B., Letellier, M., Bartol, T. M., Grillo-Bosch, D., Sejnowski, T. J., Sainlos, M., Choquet, D., Thoumine, O., & Hosy, E.
Affiliations
  • Centre National de la Recherche Scientifique (FR)
  • Salk Institute for Biological Studies (US)
  • Interdisciplinary Institute for Neuroscience, University of Bordeaux, UMR 5297, F-33000, Bordeaux, France
  • Howard Hughes Medical Institute, Salk Institute for Biological Studies, La Jolla, United States
ORCID
Venue
eLife
Publisher
eLife Sciences Publications, Ltd
Published
2018-07-25
Volume
7
ISSN
2050-084X (ISSN-L)
DOI
10.7554/elife.31755
PMC
PMC6070337
OpenAlex
W2951096450
Cited by
183
References
59
Citations by year
2026: 17 · 2025: 13 · 2024: 22 · 2023: 26 · 2022: 27 · 2021: 39 · 2020: 20 · 2019: 16 · 2018: 3
FWCI
8.88
Type
journal article
Language
en
Update notices
correction (2020-12-16)
Open access
Licence
Locations
  • eLife (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • HAL (submittedVersion, cc-by)
  • HAL Portal Artxiker (Hindustan Aeronautics Limited (India)) (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Agence Nationale de la Recherche (NanoDom)
  • Centre National de la Recherche Scientifique
  • Fondation pour la Recherche Médicale
  • H2020 European Research Council (nano-dyn-syn)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
Keywords
neuroligin-1, glutamate release, miniature EPSCs, hippocampal synapses
MeSH terms
Animals, Cells, Cultured, Female, Hippocampus, Male, Mice, Inbred C57BL, Mutation, Synaptic Transmission, Neurons, Synapses, Cell Adhesion Molecules, Neuronal, Receptors, AMPA, Excitatory Postsynaptic Potentials, Mice, Rats

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