1. Neuroscience
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Identification of a stereotypic molecular arrangement of endogenous glycine receptors at spinal cord synapses

  1. Stephanie Maynard
  2. Philippe Rostaing
  3. Natascha Schaefer
  4. Olivier Gemin
  5. Adrien Candat
  6. Andréa Dumoulin
  7. Carmen Villmann
  8. Antoine Triller
  9. Christian G Specht  Is a corresponding author
  1. Institut de Biologie de l'ENS (IBENS), PSL University, France
  2. University of Wuerzburg, Germany
  3. Inserm U1195, Université Paris-Saclay, France
Research Article
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Cite this article as: eLife 2021;10:e74441 doi: 10.7554/eLife.74441

Abstract

Precise quantitative information about the molecular architecture of synapses is essential to understanding the functional specificity and downstream signaling processes at specific populations of synapses. Glycine receptors (GlyRs) are the primary fast inhibitory neurotransmitter receptors in the spinal cord and brainstem. These inhibitory glycinergic networks crucially regulate motor and sensory processes. Thus far the nanoscale organization of GlyRs underlying the different network specificities has not been defined. Here, we have quantitatively characterized the molecular arrangement and ultra-structure of glycinergic synapses in spinal cord tissue using quantitative super-resolution correlative light and electron microscopy (SR-CLEM). We show that endogenous GlyRs exhibit equal receptor-scaffold occupancy and constant packing densities of about 2000 GlyRs µm-2 at synapses across the spinal cord and throughout adulthood, even though ventral horn synapses have twice the total copy numbers, larger postsynaptic domains and more convoluted morphologies than dorsal horn synapses. We demonstrate that this stereotypic molecular arrangement is maintained at glycinergic synapses in the oscillator mouse model of the neuromotor disease hyperekplexia despite a decrease in synapse size, indicating that the molecular organization of GlyRs is preserved in this hypomorph. We thus conclude that the morphology and size of inhibitory postsynaptic specializations rather than differences in GlyR packing determine the postsynaptic strength of glycinergic neurotransmission in motor and sensory spinal cord networks.

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Article and author information

Author details

  1. Stephanie Maynard

    Institut de Biologie de l'ENS (IBENS), PSL University, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-7838-3676
  2. Philippe Rostaing

    Institut de Biologie de l'ENS (IBENS), PSL University, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  3. Natascha Schaefer

    Institute for Clinical Neurobiology, University of Wuerzburg, Wuerzburg, Germany
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9743-1963
  4. Olivier Gemin

    Institut de Biologie de l'ENS (IBENS), PSL University, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3210-7876
  5. Adrien Candat

    Institut de Biologie de l'ENS (IBENS), PSL University, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  6. Andréa Dumoulin

    Institut de Biologie de l'ENS (IBENS), PSL University, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  7. Carmen Villmann

    Institute for Clinical Neurobiology, University of Wuerzburg, Wuerzburg, Germany
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1498-6950
  8. Antoine Triller

    Institut de Biologie de l'ENS (IBENS), PSL University, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-7530-1233
  9. Christian G Specht

    Diseases and Hormones of the Nervous System (DHNS), Inserm U1195, Université Paris-Saclay, Paris, France
    For correspondence
    christian.specht@inserm.fr
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6038-7735

Funding

H2020 European Research Council (Plastinhib)

  • Antoine Triller

Agence Nationale de la Recherche (Synaptune)

  • Antoine Triller

Agence Nationale de la Recherche (Syntrack)

  • Antoine Triller

Labex (Memolife)

  • Antoine Triller

France Bio-Imaging

  • Antoine Triller

Deutsche Forschungsgemeinschaft (VI586)

  • Carmen Villmann

Fondation pour la Recherche Médicale (SPF201809007132)

  • Stephanie Maynard

Bavarian State Ministry of Science and the Arts and the University of Würzburg (Graduate School of Life Sciences (GSLS))

  • Natascha Schaefer

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

Ethics

Animal experimentation: All experiments were in accordance with European Union guidelines and approved by the local veterinary authorities. Animals at IBENS were treated in accordance with the guidelines of the French Ministry of Agriculture and Direction Départementale des Services Vétérinaires de Paris (École Normale Supérieure, Animalerie des Rongeurs, license B 75-05-20). Procedures carried out at the Institute for Clinical Neurobiology were approved by the Veterinäramt der Stadt Würzburg and the Committee on the Ethics of Animal Experiments (Regierung von Unterfranken, Würzburg) and authorized under reference numbers 55.2-2531.01-09/14; 55.2.2-2532.2-949-31.

Reviewing Editor

  1. Julie A Kauer, Stanford University, United States

Publication history

  1. Preprint posted: September 10, 2021 (view preprint)
  2. Received: October 5, 2021
  3. Accepted: November 15, 2021
  4. Accepted Manuscript published: December 8, 2021 (version 1)
  5. Version of Record published: January 11, 2022 (version 2)
  6. Version of Record updated: January 13, 2022 (version 3)

Copyright

© 2021, Maynard 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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