The proposed studies will examine the potential role of excitatory cortical projections in regulating the activity of neurons in the striatum and substantia nigra of the rat. The influence of corticostriatal pathways and the potential intermediary role striatal nitric oxide signaling cascades on the activity states of striatal neurons and nigrostriatal dopamine cells will be investigated using extracellular and intracellular electrophysiological techniques. Additionally, discrete pharmacological manipulations of striatal neurotransmitter systems will be made in vivo via reverse dialysis and in vitro via bath perfusion to assess the potential role of nitrergic mechanisms in regulating the excitability and electrotonic coupling of striatal spiny neurons and their target neurons in the substantia nigra. It is anticipated that the neurophysiological and neuropharmacological examination of these systems at the cellular, neural network, and systems levels will provide valuable new information into the function and dysfunction of basal ganglia circuits involved in the etiology and pharmacotherapy of schizophrenia and other psychiatric disorders.
