Millions of Americans suffer from debilitating mental disorders. Most of them have motor dysfunctions as well. The pharmacological agents used to treat these patients often involve drugs thought to exert their therapeutic effects by acting on neuromodulators in the basal ganglia and the subcortical forebrain area. A common complaint concerning these drugs is the motor side effects. A more complete knowledge of the chemical circuitry of this large, complex region in the primate, would be an important contribution to the understanding of the extent to which motor and limbic systems interact and would provide a sounder basis for the development of effective pharmacological agents used for the treatment of mental disorders. The primary aim of the studies proposed here is to understand the chemical organization of the primate basal ganglia and forebrain with particular emphasis on its relationship to functional circuitry. Immunohistochemistry and tract-tracing methods will be used in combination to study the interface between the basal ganglia and the limbic system. Our points of departure are the following recent developments: 1) the striatum can be divided into a limbic-related segment and motor-related one which project topographically to the globus pallidus; 2) circuitry studies in the rat indicate that the differential peptide (enkephalin, substance P, and dynorphin) distributions in the pallidum originating from striatal cell bodies, reflect different functional (limbic vs. motor) connections; 3) the distribution patterns of the three neuropeptides in primates are markedly different from that of the rodent, which strongly indicates that the basal ganglia circuitry is distinct and more complex in primates; 4) embedded in the peptide-positive striatal efferent fibers of pallidum are large cholinergic neurons of the basal nucleus of Meynert, thus suggesting another way in which the basal ganglia can influence the limbic system. The proposed studies will: 1) examine the afferents and efferent connections of the primate globus pallidus; 2) analyze these projections with respect to function (limbic vs. motor) circuitry; 3) determine the neuropeptide involvement in these circuits; and 4) examine the interface between the basal ganglia and the limbic-related basal nucleus of Meynert.
Showing the most recent 10 out of 25 publications
