Investigating The Network-Wide Mechanisms of Pallidal Deep Brain Stimulation Using High-Density Microelectrode Arrays

Dystonia is a neurological movement disorder characterized by abnormal muscle control affecting voluntary movements and sustained postures. Although dystonia is associated with basal ganglia dysfunction, increasing evidence suggests that the cerebellum is involved in its pathophysiology. This protocol presents in vivo pallidal deep brain stimulation (DBS) in a dystonic hamster model (dt^sz hamster) combined with ex vivo high-density microelectrode array (HD-MEA) recordings to investigate cerebellar activity. The protocol includes (1) DBS surgery for electrode and stimulator implantation, (2) acute cerebellar slice preparation, (3) high-resolution electrophysiological recordings, and (4) data analysis. Representative results indicate that 11 days of pallidal DBS restored spike activity toward normal levels in the molecular, Purkinje, and granular layers, consistent with cerebellar network involvement in dystonia. This protocol enables detailed analysis of cerebellar activity and its modulation by DBS, providing a platform to investigate network-level mechanisms underlying neuromodulation therapies.