Deep brain stimulation of the pedunculopontine tegmental nucleus modulates neuronal hyperactivity and enhanced beta oscillatory activity of the subthalamic nucleus in the rat 6-hydroxydopamine model

Abstract

Deep brain stimulation (DBS) of the pedunculopontine nucleus (PPN) area has been introduced as a novel surgical therapy for dopamine refractory gait problems, freezing and postural instability in the late stage of Parkinson's disease (PD). Lesions of the pedunculopontine tegmental (PPTg) nucleus, the equivalent of the PPN in rodents, were shown to reduce the elevated discharge rate of the subthalamic nucleus (STN) in the 6-hydroxydopamine (6-OHDA) rat model of PD.In order to further elucidate the modulatory effect of the PPTg on the STN we examined the effect of 25Hz low frequency PPTg stimulation on neuronal single unit activity and oscillatory local field potentials (LFPs) of the STN, and on the electrocorticogram (ECoG) of the primary motor cortex region in rats with unilateral 6-OHDA induced nigrostriatal lesions. Stimulation of the PPTg reduced the enhanced firing rate in the STN, without affecting the firing pattern or approximate entropy (ApEn). It also reduced the activity in the beta band (15–30Hz) of the STN, which is elevated in 6-OHDA lesioned rats, without affecting beta activity in the motor cortex.We showed a modulatory effect of PPTg stimulation on altered neuronal STN activity in the PD 6-OHDA rat model, indicating that PPTg DBS may alter activity of the basal ganglia circuitry at least partially. It remains unclear, however, how these changes are exactly mediated and whether they are relevant with regard to the descending PPTg projections in the lower brainstem.