Subthalamic nucleus lesions reduce low frequency oscillatory firing of substantia nigra pars reticulata neurons in a rat model of Parkinson's disease

Single unit recordings performed in animal models of Parkinson's disease re vealed that output nuclei neurons display modifications in firing pattern a nd firing rate, which are supposed to give rise to the clinical manifestati ons of the illness. We examined the activity pattern of single units from t he substantia nigra pars reticulata, the main output nuclei of the rodent b asal ganglia, in urethane-anesthetized control and 6-hydroxydopamine-lesion ed rats (a widespread model of Parkinson's disease). We further studied the effect of a subthalamic nucleus lesion in both experimental groups. Subtha lamic nucleus lesion produces behavioral improvement in animal models of Pa rkinson's disease, and was expected to reverse the changes induced by 6-hyd roxydopamine lesions. A meticulous statistical investigation, which include d a non-biased classification of the recorded units by means of cluster ana lysis, allowed us to identify a low frequency oscillation of firing rate (s imilar to0.9 Hz) occurring in similar to 35% of the units recorded from 6-h ydroxydopamine-lesioned rats, as the main feature differentiating 6-hydroxy dopamine-lesioned and control rats. Subthalamic nucleus lesions significant ly reduced the proportion of oscillatory units in 6-hydroxydopamine-lesione d rats. However, the population of nigral units recorded from rats bearing both lesions still differed significantly from control units. These results suggest that oscillatory activity in the basal ganglia output nuclei may b e related to some clinical features of parkinsonism, and suggest a putative mechanism through which therapeutic interventions aimed at modifying subth alamic nucleus function produce clinical benefit in Parkinson's disease. (C ) 2001 Elsevier Science B.V. All rights reserved.