The basal ganglia and limbic system are considered to be anatomically and functionally separate entities, dealing with motor activity and emotion-motivation respectively. Direct projections from limbic system to basal ganglia are well described and postulated to subserve the function of motivated action. Pathways providing feedback from basal ganglia to limbic system are indirect (i.e. polysynaptic) and incompletely understood anatomically and functionally. We have recently discovered an electrophysiologic link from the substantial nigra (SN), a major output nucleus of the basal ganglia, to the dentate granule cells (DGC) of the hippocampus, a key component of the limbic system. Thus stimulation of the SN enhanced the excitability of the DGCs and the presence of norepinephrine appeared to be necessary for this enhancement to occur. The object of this proposal is to employ pharmacologic, electrophysiological, biochemical, lesion, and neuroanatomic methods to test the following hypotheses extending the preliminary findings. A) Suppression of the SN activity decreases the DGC excitability. B) Pars reticulata of the SN, and not pars compacta, is activated to enhance the DGC excitability. C) The influence of the basal ganglia on the excitability of the limbic system beyond the SN and the DGCs, to the entopeduncular nucleus, to the CA1 pyramidal cells in the hippocampus proper, and to the piriform cortical cells. D) This SN influence on the limbic system excitability is mediated through the noradrenergic system originating in locus ceruleus. We will also embark upon delineating the specific anatomic pathways underlying this functional interaction between basal ganglia and the limbic system. Specific methods employed will include microinjections, field potential and extracellular single unit recordings, and electrical stimulations under anesthesia, pharmacologic depletion of monoamines, measurements of monoamine content with HPLC with electrochemical detection, thermocoagulative lesioning techniques, and tract-tracing with immunohistochemistry. The results of these studies should provide insight into the pathways mediating basal ganglia influence on the limbic system excitability. This information should enhance understanding of the normal function of these systems and of the abnormal function in basal ganglia disorders (Huntington's or Parkinson's) and potentially in psychiatric disorders where functional anatomy may include these systems.
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