title: Stimulation of the subthalamic nucleus engages the cerebellum for motor function in parkinsonian rats.
abstract: 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.
authors.affiliation: Center for Neuropharmacology and Neuroscience, Albany Medical College, 47 New Scotland Ave, Albany, NY, 12208, USA.
authors.forename: Alexander C
authors.initials: AC
authors.lastname: Sutton
authors.affiliation: Center for Neuropharmacology and Neuroscience, Albany Medical College, 47 New Scotland Ave, Albany, NY, 12208, USA.
authors.forename: Katherine A
authors.initials: KA
authors.lastname: O'Connor
authors.affiliation: 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.
authors.forename: Julie G
authors.initials: JG
authors.lastname: Pilitsis
authors.affiliation: Center for Neuropharmacology and Neuroscience, Albany Medical College, 47 New Scotland Ave, Albany, NY, 12208, USA. shind@mail.amc.edu.
authors.forename: Damian S
authors.initials: DS
authors.lastname: Shin
mesh_terms: D000200:Action Potentials; D000818:Animals; D002531:Cerebellum / Q000503:physiopathology*; D046690:Deep Brain Stimulation; D004195:Disease Models, Animal; D008297:Male; D009474:Neurons / Q000502:physiology*; D020734:Parkinsonian Disorders / Q000503:physiopathology*; D045042:Pedunculopontine Tegmental Nucleus / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function; D020531:Subthalamic Nucleus / Q000503:physiopathology*
keywords: 6-hydroxydopamine; Forelimb akinesia; Parkinson’s disease