Unilateral lesion of the pedunculopontine nucleus induces hyperactivity in the subthalamic nucleus and substantia nigra in the rat

Abstract

Recent data suggest a role for the pedunculopontine nucleus (PPN) in the pathophysiology of Parkinson's disease. Although there is anatomical evidence that the PPN and the basal ganglia are reciprocally connected, the functional importance of these connections is poorly understood. Lesioning of the PPN was shown to induce akinesia in primates, whereas in the 6-hydroxydopamine rat model the PPN was found to be hyperactive. As both nigrostriatal dopamine depletion and lesioning of the PPN were shown to induce akinesia and parkinsonism, the present study was performed in order to investigate the changes in neuronal activity of the subthalamic nucleus (STN) and the substantia nigra pars reticulata (SNr) after unilateral ibotenic acid lesioning of the PPN and after unilateral 6-hydroxydopamine lesioning of the substantia nigra pars compacta (SNc). The firing rate of STN neurones significantly increased from 10.2 +/- 6.2 (mean +/- SD) to 14.6 +/- 11.7 spikes/s after lesion of the PPN and to 18.6 +/- 14.5 spikes/s after lesion of the SNc. The activity of the SNr significantly increased from 19.6 +/- 10.5 to 28.7 +/- 13.4 spikes/s after PPN lesioning and to 23.5 +/- 10.8 spikes/s after SNc lesioning. Furthermore, PPN lesion decreased the number of spontaneously firing dopaminergic SNc cells, while having no effect on their firing rate. The results of our study show that lesion of the PPN leads to hyperactivity of the STN and SNr, similar to the changes induced by lesion of the SNc. Moreover, the decreased activity of SNc cells observed after PPN lesion might be at the origin of activity changes in the STN and SNr.