Interactions and Influences of Spinal Modulatory Systems in Health and in Amyotrophic Lateral Sclerosis

Abstract

The goal of this thesis was to better understand the influences of neuromodulatory systems and the interactions that occur between them. We studied the spinal V0c interneurons and brainstem serotonergic modulatory systems using mice, locomotion, and amyotrophic lateral sclerosis as models. Our results show that multiple modulatory systems provide the flexibility needed to support a wide range of behaviours, enabling compensatory mechanisms within these systems, such as in instances where one modulatory system is compromised, or in cases of motor disease. However, we also show that such compensation is not always beneficial, such as in the context of amyotrophic lateral sclerosis. Overall, our work has deepened our understanding of the roles and interactions of modulatory systems, notably in the context of motor diseases like amyotrophic lateral sclerosis, which we hope will contribute to the development of more effective therapies within and beyond the motor system.