Stimulation of the subthalamic nucleus engages the cerebellum for motor function in parkinsonian rats.

Autor: Sutton AC; Center for Neuropharmacology and Neuroscience, Albany Medical College, 47 New Scotland Ave, Albany, NY, 12208, USA., O'Connor KA; Center for Neuropharmacology and Neuroscience, Albany Medical College, 47 New Scotland Ave, Albany, NY, 12208, USA., Pilitsis JG; Center for Neuropharmacology and Neuroscience, Albany Medical College, 47 New Scotland Ave, Albany, NY, 12208, USA.; Division of Neurosurgery, Albany Medical Center, 47 New Scotland Ave, Albany, NY, 12208, USA., Shin DS; Center for Neuropharmacology and Neuroscience, Albany Medical College, 47 New Scotland Ave, Albany, NY, 12208, USA. shind@mail.amc.edu.
Jazyk: angličtina
Zdroj: Brain structure & function [Brain Struct Funct] 2015 Nov; Vol. 220 (6), pp. 3595-609. Date of Electronic Publication: 2014 Aug 15.
DOI: 10.1007/s00429-014-0876-8
Abstrakt: Deep brain stimulation (DBS) is effective in managing motor symptoms of Parkinson's disease in well-selected individuals. Recently, research has shown that DBS in the basal ganglia (BG) can alter neural circuits beyond the traditional basal ganglia-thalamus-cortical (BG-TH-CX) loop. For instance, functional imaging showed alterations in cerebellar activity with DBS in the subthalamic nucleus (STN). However, these imaging studies revealed very little about how cell-specific cerebellar activity responds to STN stimulation or if these changes contribute to its efficacy. In this study, we assess whether STN-DBS provides efficacy in managing motor symptoms in Parkinson's disease by recruiting cerebellar activity. We do this by applying STN-DBS in hemiparkinsonian rats and simultaneously recording neuronal activity from the STN, brainstem and cerebellum. We found that STN neurons decreased spiking activity by 55% during DBS (P = 0.038), which coincided with a decrease in most pedunculopontine tegmental nucleus and Purkinje neurons by 29% (P < 0.001) and 28% (P = 0.003), respectively. In contrast, spike activity in the deep cerebellar nuclei increased 45% during DBS (P < 0.001), which was likely from reduced afferent activity of Purkinje cells. Then, we applied STN-DBS at sub-therapeutic current along with stimulation of the deep cerebellar nuclei and found similar improvement in forelimb akinesia as with therapeutic STN-DBS alone. This suggests that STN-DBS can engage cerebellar activity to improve parkinsonian motor symptoms. Our study is the first to describe how STN-DBS in Parkinson's disease alters cerebellar activity using electrophysiology in vivo and reveal a potential for stimulating the cerebellum to potentiate deep brain stimulation of the subthalamic nucleus.
Databáze: MEDLINE