Neuroscience Program, University of California, San Francisco, San Francisco, United States; Kavli Institute for Fundamental Neuroscience, University of California, San Francisco, United States; Weill Institute for Neuroscience, University of California,, San Francisco, United States
Isabelle Gonzalez Montalvo
Neuroscience Program, University of California, San Francisco, San Francisco, United States; Kavli Institute for Fundamental Neuroscience, University of California, San Francisco, United States; Weill Institute for Neuroscience, University of California,, San Francisco, United States
Perry WE Spratt
Neuroscience Program, University of California, San Francisco, San Francisco, United States; Kavli Institute for Fundamental Neuroscience, University of California, San Francisco, United States; Weill Institute for Neuroscience, University of California,, San Francisco, United States
Rea J Brakaj
Kavli Institute for Fundamental Neuroscience, University of California, San Francisco, United States; Weill Institute for Neuroscience, University of California,, San Francisco, United States; Department of Neurology, University of California, San Francisco, San Francisco, United States
Jasmine A Stansil
Kavli Institute for Fundamental Neuroscience, University of California, San Francisco, United States; Weill Institute for Neuroscience, University of California,, San Francisco, United States; Department of Neurology, University of California, San Francisco, San Francisco, United States; Aligning Science Across Parkinson’s (ASAP) Collaborative Research Network, Chevy Chase, United States
Emily L Twedell
Neuroscience Program, University of California, San Francisco, San Francisco, United States; Kavli Institute for Fundamental Neuroscience, University of California, San Francisco, United States; Weill Institute for Neuroscience, University of California,, San Francisco, United States; Aligning Science Across Parkinson’s (ASAP) Collaborative Research Network, Chevy Chase, United States
Neuroscience Program, University of California, San Francisco, San Francisco, United States; Kavli Institute for Fundamental Neuroscience, University of California, San Francisco, United States; Weill Institute for Neuroscience, University of California,, San Francisco, United States; Department of Neurology, University of California, San Francisco, San Francisco, United States
Neuroscience Program, University of California, San Francisco, San Francisco, United States; Kavli Institute for Fundamental Neuroscience, University of California, San Francisco, United States; Weill Institute for Neuroscience, University of California,, San Francisco, United States; Department of Neurology, University of California, San Francisco, San Francisco, United States; Aligning Science Across Parkinson’s (ASAP) Collaborative Research Network, Chevy Chase, United States
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.
