Substantia nigra pars reticulata units in 6-hydroxydopamine-lesioned rats:responses to striatal D2 dopamine receptor stimulation and subthalamic lesions

In order to increase our understanding of Parkinson's disease pathophysiolo gy, we studied the effects of intrastriatally administered selective dopami ne receptor agonists on single units from the substantia nigra pars reticul ata of 6-hydroxydopamine (6-OHDA)-lesioned rats with or without an addition al subthalamic nucleus lesion. Nigral pars reticulata units of 6-OHDA-lesio ned rats were classified into two types, showing regular and bursting disch arge patterns, respectively ('non-burst' and 'burst' units). Non-burst and burst units showed distinct responses to intrastriatal quinpirole (the form er were excited and burst units inhibited). Furthermore, subthalamic nucleu s lesions significantly decreased the number of nigral units showing a spon taneous bursting pattern, and reduced the proportion of units that responde d to quinpirole. In contrast, subthalamic lesions did not alter the proport ion of nigral units that responded to SKF38393, although the lesions change d some response features, e.g. response type and magnitude. Burst analysis showed that quinpirole did not modify the discharge pattern of burst units, whereas SKF38393 produced a shift to regular firing in 62% of the burst un its tested. In conjunction, our results support that. (i) the subthalamic n ucleus has an important influence on output nuclei firing pattern; (ii) str iatal D2 receptors have a strong influence on nigral firing rate, and a les s relevant role in controlling firing pattern; (iii) burst and non-burst un its differ in their response to selective stimulation of striatal dopamine receptors; (iv) the effects of striatal D2 receptors on nigral units are ma inly, though not exclusively, mediated by the subthalamic nucleus; and (v) nigral responses to SKF38393 involve the subthalamic nucleus.