The goal of this competitive renewal is to understand the effects of dopamine on cells in the substantia nigra pars reticulata, a primary output nucleus of the basal ganglia.
Four specific aims with a total of 12 experiments are outlined: The experiments outlined under Aim 1 will selectively activate D1 and/or D2 receptors in the striatum of the rat. Recordings will reveal the effects on discharge in the SNr, and behavioral studies will evaluate the overall effects in the intact awake rat.
Aim 2 will attempt to determine differential effects of the direct versus indirect pathways from striatum to SNr. Basically the same set of experiments as proposed under Aim 1 will be repeated in rats with lesions of the subthalamic nucleus, which should eliminate influences of the indirect pathway on SNr.
Aim 3 will use the same striatal stimulation paradigm as Aim 1, but local blockade of D1 and/or D2 receptors within SNr will also be made. Thus the effects of local receptor blockade on SNr discharge and behavior will be evaluated.
Specific Aim 4 will determine whether or not nigral or pallidal projecting neurons in the striatum express functional D2 receptors. The study will utilize patch-clamp recordings on dissociated striatal neurons that have been prelabeled by retrograde transport of fluorescent beads. The patch clamp electrode will contain the D2 agonist quinpirole so that D2 activated channels will be detected.
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