Clinically, damage to the basal ganglia can result in serious disorders of movement. One of these disorders, Parkinson's disease, stems from a loss of dopaminergic basal ganglia afferents. Therefore, it is important to understand dopamine's influence on the functioning of the basal ganglia. Dopaminergic control of the so-called """"""""indirect"""""""" basal ganglia pathway is less well characterized than for the """"""""direct"""""""" pathway. Expression of immediately gene (IEG) protein is a common technique for immunocytochemically assaying cellular activity ex vivo. The proposed studies will examine IEG protein expression induced by dopaminergic drugs in each nucleus of the indirect pathway of rats. Previous studies have described D2 receptor control over globus pallidus neurons and striatopallidal neurons. The proposed studies will characterize D1 receptor effects as well as D1/D2 receptor interactions concerning IEG expression in these cells. They will also examine the effects of lesions of the mesotelencephalic dopaminergic system (an animal model for Parkinson's disease). IEG expression in the other nuclei of the indirect pathway has only been described in a preliminary fashion. The proposed experiments characterize the D1 and D2 receptor influences on IEG expression in these nuclei. The studies involving the subthalamic nucleus and the thalamic reticular nucleus may provide particularly novel findings. These experiments should provide valuable insight into both the normal regulation of the indirect basal ganglia pathway by dopamine as well as this regulation under conditions of dopaminergic denervation.
