Implication of regional selectivity of dopamine deficits in impaired suppressing of involuntary movements in Parkinson's disease

Abstract

To improve the initiation and speed of intended action, one of the crucial mechanisms is suppressing unwanted movements that interfere with goal-directed behavior, which is observed relatively aberrant in Parkinson's disease patients. Recent research has highlighted that dopamine deficits in Parkinson's disease predominantly occur in the caudal lateral part of the substantia nigra pars compacta (SNc) in human patients. We previously found two parallel circuits within the basal ganglia, primarily divided into circuits mediated by the rostral medial part and caudal lateral part of the SNc dopamine neurons. We have further discovered that the indirect pathway in caudal basal ganglia circuits, facilitated by the caudal lateral part of the SNc dopamine neurons, plays a critical role in suppressing unnecessary involuntary movements when animals perform voluntary goal-directed actions. We thus explored recent research in humans and non-human primates focusing on the distinct functions and networks of the caudal lateral part of the SNc dopamine neurons to elucidate the mechanisms involved in the impairment of suppressing involuntary movements in Parkinson's disease patients.