Cortical Circuit Dysfunction as a Potential Driver of Amyotrophic Lateral Sclerosis

Aurore Brunet, Geoffrey Stuart-Lopez, Thibaut Burg, Jelena Scekic-Zahirovic, Caroline Rouaux
2020 Frontiers in Neuroscience  
Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease that affects selected cortical and spinal neuronal populations, leading to progressive paralysis and death. A growing body of evidences suggests that the disease may originate in the cerebral cortex and propagate in a corticofugal manner. In particular, transcranial magnetic stimulation studies revealed that ALS patients present with early cortical hyperexcitability arising from a combination of increased
more » ... and decreased inhibition. Here, we discuss the possibility that initial cortical circuit dysfunction might act as the main driver of ALS onset and progression, and review recent functional, imaging and transcriptomic studies conducted on ALS patients, along with electrophysiological, pathological and transcriptomic studies on animal and cellular models of the disease, in order to evaluate the potential cellular and molecular origins of cortical hyperexcitability in ALS.
doi:10.3389/fnins.2020.00363 pmid:32410944 pmcid:PMC7201269 fatcat:66cevdajb5bkrjhd3mcxbr5ssa