Patients with diseases of the basal ganglia have a number of debilitating disorders that involve a combination of motoric, cognitive, and emotional symptoms. The basal ganglia are a set of structures known for their interconnectivity, and loops systems. Based on the anatomy and physiology of the motor loops, it has been suggested that the basal ganglia and frontal cortex are organized in parallel, functionally segregated circuits. Each circuit involves a specific, functionally distinct region of the frontal cortex and projects to anatocally distinct sectors of the striatum, the pallidum, the substantia nigra, and the thalamus. Our anatomical work has suggested ways in which the ventral (or limbic-related parts of the basal ganglia) may interface with the motor circuits to produce the constellation of symptoms seen in basal ganglia diseases. The main objective of this proposal is to test this idea and to further define the role of the ventral basal ganglia in modulating general basal ganglia output by the anatomical pathways involved. In particular, our results show that: the dorsal striatum may be modulated by inputs from the ventral striatum and ventral pallidum. In addition, unlike rats, the main efferent projection of the ventral pallidum, outside of basal ganglia structures is not to the thalamus but to the lateral habenular nucleus. The source of these fibers is controversial but is likely to be derived from the ventral striatum. The connections of this nucleus are therefore important to know in order to understand how information flows through the ventral basal ganglia. Finally, enkephalin immunoreactivity is dense in the substantia nigra, pars reticulata. The source of these fibers is controversial but is likely to be derived from the ventral striatum. We will use intracellular injections and circuit tracing techniques to identify pathways, and immunohistochemistry and in situ hybridization to colocalize relevant transmitters in particular pathways. Tracers will be injected to study: the extent to which the ventral pallidum and ventral striatum anatomically modulates the dorsal striatum; the connections of the lateral habenular nucleus; and whether there is an enkephalinergic projection from the ventral striatum to the substantia nigra.
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