BASALGANGLIANETWORKS · Basal ganglia and the control of locomotion

The goal of this project is to understand of the mechanisms, at the neuronal network level, by which the basal ganglia control locomotor activity. The rational beyond this objective is twofold. First, altered locomotor activity is a hallmark of motor and psychiatric disorders. Second, the basal ganglia, a group of subcortical nuclei that connects the entire neocortex to locomotor brain centers, are known to control locomotion, but the network mechanisms responsible for this function are still unclear. Overall this project will have a strong impact on the understanding of an essential brain function (the control of locomotion by basal ganglia) and has direct implication for widespread human diseases such as Parkinson Disease, schizophrenia and drug addiction To reach this goal we will use an experimental strategy that combines state-of-art large-scale electrophysiological tools (silicon-based electrode arrays) and pharmacological manipulations of the locomotion, using rats as experimental model. Specifically the applicant proposes to investigate the mechanism by which low dose of cannabinoids increase spontaneous locomotor activity. The highest level of cannabinoid receptors in the brain have been reported in basal ganglia nuclei that belong to two pathways (the so called direct and indirect pathways) which are classically believed to have antagonistically impact on locomotor activity. How low doses of cannabinoid can affect both direct and indirect pathways and result in increased locomotor activity is therefore puzzling. We hypothesize that solving this apparent contradiction will significantly advance the understanding of the neuronal mechanisms that control locomotion. Moreover as the endocannabinoid system has been implicated in numerous basal ganglia-related diseases, the insight generated by this project will provide new therapeutic strategies to treat widespread diseases such as drug addiction and Parkinson’s disease.