Alpha2-Containing Glycine Receptors Promote Neonatal Spontaneous Activity of Striatal Medium Spiny Neurons and Support Maturation of Glutamatergic Inputs

Joris Comhair; Jens Devoght; Giovanni Morelli; Robert J Harvey; Victor Briz; Sarah C Borrie; Claudia Bagni; Jean-Michel Rigo; Serge N Schiffmann; David Gall; Bert Brone; Svetlana M Molchanova

doi:10.3389/fnmol.2018.00380

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Alpha2-Containing Glycine Receptors Promote Neonatal Spontaneous Activity of Striatal Medium Spiny Neurons and Support Maturation of Glutamatergic Inputs

Journal article

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Alpha2-Containing Glycine Receptors Promote Neonatal Spontaneous Activity of Striatal Medium Spiny Neurons and Support Maturation of Glutamatergic Inputs

Joris Comhair, Jens Devoght, Giovanni Morelli, Robert J Harvey, Victor Briz, Sarah C Borrie, Claudia Bagni, Jean-Michel Rigo, Serge N Schiffmann, David Gall, …

Frontiers in Molecular Neuroscience, Vol.11(380), pp.1-16

2018

DOI: https://doi.org/10.3389/fnmol.2018.00380

PMCID: PMC6196267

PMID: 30374290

Appears in UniSC Diversity and Inclusion Research Collection

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Abstract

autism spectrum disorders

dorsal striatum

medium spiny neurons

glycine receptors

spontaneous activity

synaptic development

UniSC Diversity Area - Disability and Inclusion

Glycine receptors (GlyRs) containing the a2 subunit are highly expressed in the developing brain, where they regulate neuronal migration and maturation, promote spontaneous network activity and subsequent development of synaptic connections. Mutations in GLRA2 are associated with autism spectrum disorder, but the underlying pathophysiology is not described yet. Here, using Glra2-knockout mice, we found a GlyR-dependent effect on neonatal spontaneous activity of dorsal striatum medium spiny neurons (MSNs) and maturation of the incoming glutamatergic innervation. Our data demonstrate that functional GlyRs are highly expressed in MSNs of one-week-old mice, but they do not generate endogenous chloride-mediated tonic or phasic current. Despite of that, knocking out the Glra2 severely affects the shape of action potentials and impairs spontaneous activity and the frequency of miniature AMPA receptormediated currents in MSNs. This reduction in spontaneous activity and glutamatergic signaling can attribute to the observed changes in neonatal behavioral phenotypes as seen in ultrasonic vocalizations and righting reflex. In adult Glra2-knockout animals, the glutamatergic synapses in MSNs remain functionally underdeveloped. The number of glutamatergic synapses and release probability at presynaptic site remain unaffected, but the amount of postsynaptic AMPA receptors is decreased. This deficit is a consequence of impaired development of the neuronal circuitry since acute inhibition of GlyRs by strychnine in adult MSNs does not affect the properties of glutamatergic synapses. Altogether, these results demonstrate that GlyR-mediated signaling supports neonatal spontaneous MSN activity and, in consequence, promotes the functional maturation of glutamatergic synapses on MSNs. The described mechanism might shed light on the pathophysiological mechanisms in GLRA2-linked autism spectrum disorder cases.

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Title: Alpha2-Containing Glycine Receptors Promote Neonatal Spontaneous Activity of Striatal Medium Spiny Neurons and Support Maturation of Glutamatergic Inputs
Authors: Joris Comhair (Author) - Université Libre de Bruxelles
Jens Devoght (Author) - Hasselt University
Giovanni Morelli (Author) - Hasselt University
Robert J Harvey (Author) - University of the Sunshine Coast - Faculty of Science, Health, Education and Engineering
Victor Briz (Author) - KU Leuven
Sarah C Borrie (Author) - KU Leuven
Claudia Bagni (Author) - KU Leuven
Jean-Michel Rigo (Author) - Hasselt University
Serge N Schiffmann (Author) - Université Libre de Bruxelles
David Gall (Author) - Université Libre de Bruxelles
Bert Brone (Author) - Hasselt University
Svetlana M Molchanova (Author) - Université Libre de Bruxelles
Publication details: Frontiers in Molecular Neuroscience, Vol.11(380), pp.1-16
Publisher: Frontiers Research Foundation
Date published: 2018
DOI: 10.3389/fnmol.2018.00380
ISSN: 1662-5099
PMID: 30374290; PMC6196267
Copyright note: Copyright © 2018 Comhair, Devoght, Morelli, Harvey, Briz, Borrie, Bagni, Rigo, Schiffmann, Gall, Brône and Molchanova. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
Organisation Unit: School of Health; School of Health and Sport Sciences - Legacy; Centre for Bioinnovation; School of Health and Behavioural Sciences - Legacy
Language: English
Record Identifier: 99451000202621
Output Type: Journal article

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Collaboration types: Domestic collaboration; International collaboration
Web Of Science research areas: Neurosciences

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