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

  1. Kalina T Haas
  2. Benjamin Compans
  3. Mathieu Letellier
  4. Thomas M Bartol
  5. Dolors Grillo-Bosch
  6. Terrence J Sejnowski
  7. Matthieu Sainlos
  8. Daniel Choquet
  9. Olivier Thoumine
  10. Eric Hosy  Is a corresponding author
  1. Université de Bordeaux, France
  2. Howard Hughes Medical Institute, Salk Institute for Biological Studies, United States
Research Article
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Cite this article as: eLife 2018;7:e31755 doi: 10.7554/eLife.31755

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 machineries alignment 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 ~100nm 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.

Article and author information

Author details

  1. Kalina T Haas

    Interdisciplinary Institute for Neuroscience, Université de Bordeaux, Bordeaux, France
    Competing interests
    The authors declare that no competing interests exist.
  2. Benjamin Compans

    Interdisciplinary Institute for Neuroscience, Université de Bordeaux, Bordeaux, France
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7823-1499
  3. Mathieu Letellier

    Interdisciplinary Institute for Neuroscience, Université de Bordeaux, Bordeaux, France
    Competing interests
    The authors declare that no competing interests exist.
  4. Thomas M Bartol

    Howard Hughes Medical Institute, Salk Institute for Biological Studies, La Jolla, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Dolors Grillo-Bosch

    Interdisciplinary Institute for Neuroscience, Université de Bordeaux, Bordeaux, France
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8695-5718
  6. Terrence J Sejnowski

    Howard Hughes Medical Institute, Salk Institute for Biological Studies, La Jolla, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0622-7391
  7. Matthieu Sainlos

    Interdisciplinary Institute for Neuroscience, Université de Bordeaux, Bordeaux, France
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5465-5641
  8. Daniel Choquet

    Interdisciplinary Institute for Neuroscience, Université de Bordeaux, Bordeaux, France
    Competing interests
    The authors declare that no competing interests exist.
  9. Olivier Thoumine

    Interdisciplinary Institute for Neuroscience, Université de Bordeaux, Bordeaux, France
    Competing interests
    The authors declare that no competing interests exist.
  10. Eric Hosy

    Interdisciplinary Institute for Neuroscience, Université de Bordeaux, Bordeaux, France
    For correspondence
    eric.hosy@u-bordeaux.fr
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2479-5915

Funding

Agence Nationale de la Recherche (NanoDom)

  • Mathieu Letellier
  • Daniel Choquet
  • Olivier Thoumine
  • Eric Hosy

Centre National de la Recherche Scientifique

  • Mathieu Letellier
  • Matthieu Sainlos
  • Daniel Choquet
  • Olivier Thoumine
  • Eric Hosy

Fondation pour la Recherche Médicale

  • Benjamin Compans

H2020 European Research Council (nano-dyn-syn)

  • Kalina T Haas
  • Benjamin Compans
  • Dolors Grillo-Bosch
  • Matthieu Sainlos
  • Daniel Choquet
  • Eric Hosy

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: These experiments have been conducted in France, the rat Ratus norvegicus, in accordance with directive 86/609/EEC of 19 October 1986, on the protection of animals used for experimental and other scientific purposes. It was followed in France by 3 rulings in 1987, 2001, 2005 (article R214-87 and R214-130 of the rural code) and 3 rulings of 19 April 1988. An ethical system complemented this regulation since 2008, with harmonization of the commitments between the private and the public sector, by the signature of the National Charter for ethical animal experimentation by institutions in animal experimentation ethics (EAA) and by the CNREEA (Centre national of ethical reflection on animal experiments). Our projects are therefore assessed by the Ethics Committee No 50 of Bordeaux attached to the CNREEA. Thanks to our preparation, we will be ready to apply from January 1St, 2013, the 63-2010-EU directive which transcribed in French law will be published on November 12, 2012 in the form of 2 decree (Code Rural R214-87 to 138) and 4 bylaws.

Reviewing Editor

  1. Gary L Westbrook, Vollum Institute, United States

Publication history

  1. Received: September 5, 2017
  2. Accepted: July 24, 2018
  3. Accepted Manuscript published: July 25, 2018 (version 1)
  4. Version of Record published: August 1, 2018 (version 2)

Copyright

© 2018, Haas et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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