Relaxation of synaptic inhibitory events as a compensatory mechanism in fetal SOD spinal motor networks
- Université de Bordeaux, CNRS, France
Abstract
Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease affecting motor neurons (MNs) during late adulthood. Here, with the aim of identifying early changes underpinning ALS neurodegeneration, we analyzed the GABAergic/glycinergic inputs to E17.5 fetal MNs from SOD1G93A (SOD) mice in parallel with chloride homeostasis. Our results show that IPSCs are less frequent in SOD animals in accordance with a reduction of synaptic VIAAT-positive terminals. SOD MNs exhibited an EGABAAR 10 mV more depolarized than in WT MNs associated with a KCC2 reduction. Interestingly, SOD GABAergic/glycinergic IPSCs and evoked GABAAR-currents exhibited a slower decay correlated to elevated [Cl-]i. Computer simulations revealed that a slower relaxation of synaptic inhibitory events acts as compensatory mechanism to strengthen GABA/glycine inhibition when EGABAAR is more depolarized. How such mechanisms evolve during pathophysiological processes remain to be determined, but our data indicate that at least SOD1 familial ALS may be considered as a neurodevelopmental disease.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting files.
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Author details
Pascal Branchereau
Funding
Federation pour la Recherche sur le Cerveau
- Pascal Branchereau
Association pour la Recherche sur la Sclérose Latérale Amyotrophique et autres Maladies du Motoneurone
- Pascal Branchereau
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 procedures were carried out in accordance with the local ethics committee of the University of Bordeaux (Saisine SOD1G093A - APAFiS #19366) and European Committee Council directives. All efforts were made to minimize animal suffering and reduce the number of animals used.
Copyright
© 2019, Branchereau 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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Relaxation of synaptic inhibitory events as a compensatory mechanism in fetal SOD spinal motor networks
eLife 8:e51402.
https://doi.org/10.7554/eLife.51402
