Neuropathology of the basal ganglia has been clearly demonstrated of implicated in a number of debilitating disorders that involve motor, and emotional deficits, including Parkinson's disease, and Huntington's disease. The basal ganglia is a set of structures well known for their interconnectivity and their 'loop' systems, which have been associated with different cortical functions. The pathways through the basal ganglia of the limbic loop have not been as well identified as the corresponding pathways of the motor loop. The main objective of this proposal is to identify these pathways and the extent to which they are integrated with those of the motor system. A through knowledge of the circuitry of the basal ganglia and the potential integration between motor- and limbic- related pathways will contribute to a better understanding of basal ganglia organization and of the constellation of clinical symptoms in diseases affecting these structures. Electrophysiological and circuit tracing techniques will be used to identify pathways and immunocytochemical methods to identify transmitter systems. By electrophysiological mapping techniques, anterograde tracers will be placed into limbic-related pallidal regions (or those regions known to receive input from the limbic-innervated striatum). Terminal fields from these injections will be compared to those originating in motor-related pallidum. Retrograde tracers will be placed in the regions of the striatum known to receive input from either limbic- or motor- related cortical regions and the distribution of midbrain dopamine cells projecting to these regions will be charted to determine whether these functionally different striatal regions input from subpopulations of dopamine neurons. Finally, the distributions of neurotransmitter systems in animals and human ganglia will be compared. These studies will contribute to the understanding of the organization of these structures in the human.
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