Relaxation of synaptic inhibitory events as a compensatory mechanism in fetal SOD spinal motor networks.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 31868588.
- Also identified by DOI 10.7554/eLife.51402 and PMC identifier 6974356.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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 SOD1<sup>G93A</sup> (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 E<sub>GABAAR</sub>10 mV more depolarized than in WT MNs associated with a KCC2 reduction. Interestingly, SOD GABAergic/glycinergic IPSCs and evoked GABA<sub>A</sub>R-currents exhibited a slower decay correlated to elevated [Cl<sup>-</sup>]<sub>i</sub>. Computer simulations revealed that a slower relaxation of synaptic inhibitory events acts as compensatory mechanism to strengthen GABA/glycine inhibition when E<sub>GABAAR</sub> 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.
Medical subject headings
- Amyotrophic Lateral Sclerosis
- GABAergic Neurons
- Motor Neurons
- Superoxide Dismutase-1