The contribution of spinal inhibitory circuits to aberrant excitability in Amyotrophic Lateral Sclerosis

Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disease characterized by death of cells located in the spinal cord that control muscle function (motoneurons), resulting in weakness and death. Motoneurons form complex neuronal circuits with other cells in the spinal cord (interneurons) to ensure effective muscle contraction. Supported by preliminary data, I hypothesize that these circuits are affected in ALS and could contribute to motoneuron death. The aim of this project is to understand how such circuits are affected in ALS and how these abnormalities contribute to the disease. I will use two genetically modified mouse models with ALS-inducing human mutated genes, perform electrical recordings from motoneurons and characterize gene expression abnormalities both in interneurons and motoneurons. This project will reveal early alterations in specific circuits, which could shift our understanding of ALS and provide a mean for early diagnosis which could potentially lead to earlier and more efficient treatment.