Therapeutic deep brain stimulation disrupts movement-related subthalamic nucleus activity in parkinsonian mice

Subthalamic nucleus deep brain stimulation (STN DBS) relieves many motor symptoms of Parkinson's disease (PD), but its underlying therapeutic mechanisms remain unclear. Since its advent, three major theories have been proposed: (1) DBS inhibits the STN and basal ganglia output; (2) DBS antidromically activates motor cortex; and (3) DBS disrupts firing dynamics within the STN. Previously, stimulation-related electrical artifacts limited mechanistic investigations using electrophysiology. We used electrical artifact-free GCaMP fiber photometry to investigate activity in basal ganglia nuclei during STN DBS in parkinsonian mice. To test whether the observed changes in activity were sufficient to relieve motor symptoms, we then combined electrophysiological recording with targeted optical DBS protocols. Our findings suggest that STN DBS exerts its therapeutic effect through the disruption of movement-related STN activity, rather than inhibition or antidromic activation. These results provide insight into optimizing PD treatments and establish an approach for investigating DBS in other neuropsychiatric conditions.

Automated summary

This study investigated the therapeutic effects and underlying mechanisms of subthalamic nucleus deep brain stimulation (STN DBS) in Parkinson's disease mice. The results suggest that STN DBS exerts its therapeutic effects through disrupting movement-related activity in the subthalamic nucleus. These findings provide new insights for optimizing Parkinson's disease treatments and offer an approach for studying deep brain stimulation in other neuropsychiatric conditions.