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

Stephanie A Maynard, Philippe Rostaing, Natascha Schaefer, View ORCID ProfileOlivier Gemin, Adrien Candat, Andréa Dumoulin, Carmen Villmann, View ORCID ProfileAntoine Triller, View ORCID ProfileChristian G Specht
doi: https://doi.org/10.1101/2021.09.09.459599
Stephanie A Maynard
1Institut de Biologie de l’ENS (IBENS), Ecole Normale Supérieure, CNRS, Inserm, Université PSL, Paris, France
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Philippe Rostaing
1Institut de Biologie de l’ENS (IBENS), Ecole Normale Supérieure, CNRS, Inserm, Université PSL, Paris, France
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Natascha Schaefer
2Institute for Clinical Neurobiology, University Hospital, Julius-Maximilians-University, Würzburg, Germany
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Olivier Gemin
1Institut de Biologie de l’ENS (IBENS), Ecole Normale Supérieure, CNRS, Inserm, Université PSL, Paris, France
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Adrien Candat
1Institut de Biologie de l’ENS (IBENS), Ecole Normale Supérieure, CNRS, Inserm, Université PSL, Paris, France
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Andréa Dumoulin
1Institut de Biologie de l’ENS (IBENS), Ecole Normale Supérieure, CNRS, Inserm, Université PSL, Paris, France
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Carmen Villmann
2Institute for Clinical Neurobiology, University Hospital, Julius-Maximilians-University, Würzburg, Germany
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Antoine Triller
1Institut de Biologie de l’ENS (IBENS), Ecole Normale Supérieure, CNRS, Inserm, Université PSL, Paris, France
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  • For correspondence: christian.specht@inserm.fr triller@biologie.ens.fr
Christian G Specht
1Institut de Biologie de l’ENS (IBENS), Ecole Normale Supérieure, CNRS, Inserm, Université PSL, Paris, France
3Diseases and Hormones of the Nervous System (DHNS), Inserm, Université Paris-Saclay, Le Kremlin-Bicêtre, Paris, France
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  • ORCID record for Christian G Specht
  • For correspondence: christian.specht@inserm.fr triller@biologie.ens.fr
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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.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • This version of the manuscript has been revised to respond to the comments of the external review commissioned by Review Commons (4 external reviewers).

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC 4.0 International license.
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Posted September 13, 2021.
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Identification of a stereotypic molecular arrangement of endogenous glycine receptors at spinal cord synapses
Stephanie A Maynard, Philippe Rostaing, Natascha Schaefer, Olivier Gemin, Adrien Candat, Andréa Dumoulin, Carmen Villmann, Antoine Triller, Christian G Specht
bioRxiv 2021.09.09.459599; doi: https://doi.org/10.1101/2021.09.09.459599
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Identification of a stereotypic molecular arrangement of endogenous glycine receptors at spinal cord synapses
Stephanie A Maynard, Philippe Rostaing, Natascha Schaefer, Olivier Gemin, Adrien Candat, Andréa Dumoulin, Carmen Villmann, Antoine Triller, Christian G Specht
bioRxiv 2021.09.09.459599; doi: https://doi.org/10.1101/2021.09.09.459599

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