Research is proposed which will investigate information processing in input (caudate nucleus) and output (entopeduncular nucleus, globus pallidus) areas of the basal ganglia of cats exposed to the dOpaminergic toxin N-methyl-4-phenyl-1,2,3,6- tetrahydropyridine (MPTP). Following MPTP administration, cats acutely become akinetic, freeze during movement, and have drastically reduced responsiveness to various types of external stimulation. This distinct behavioral syndrome is accompanied by a greater than 90% striatal dopamine depletion and loss of substantia nigra pars compacta neurons. Over the course of several weeks to months, cats enter into subacute and chronic phases of this syndrome during which time gross motor behavior approximates normal while substantia nigra pathology remains extensive and striatal dopamine loss is greater than 70% The presently proposed research is designed to investigate electrophysiological, biochemical, and behavioral aspects of MPTP-induced nigrostriatal damage and the resultant recovery of this system over time. Chronic extracellular single unit recordings will allow examination of spontaneous neural activity, response to stimulation of afferent brain structures and sensory information processing in basal ganglia input and output structures under normal circumstances and at various phases of the MPTP-induced behavioral syndrome. Physiological findings will be correlated with results from detailed neurological and behavioral testing. Additionally, some of the possible neurochemical mechanisms leading to behavioral recovery will be assessed chronically by examining levels of catecholamine metabolites in CSF through the different phases of the MPTP syndrome and by examining the state of pre- and post-synaptic mechanisms in the striatum. These experiments should provide useful information on the functioning of the impaired basal ganglia and give insight into how the dopamine depleted basal ganglia responds to and processes inputs and what these responses mean for behavior. Information on the compensatory mechanisms leading to behavioral recovery following damage to the nigrostriatal system could have relevance for understanding the pathophysiology Parkinson's disease.
Showing the most recent 10 out of 23 publications
