Therapeutic Deep Brain Stimulation Disrupts Subthalamic Nucleus Activity Dynamics in Parkinsonian Mice
Therapeutic Deep Brain Stimulation Disrupts Subthalamic Nucleus Activity Dynamics in Parkinsonian Mice
Abstract 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 calcium imaging 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 STN dynamics, 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.
Stansil Jasmine A、Bender Kevin J、Nelson Alexandra B、Schor Jonathan S、Montalvo Isabelle Gonzalez、Brakaj Rea J、Spratt Perry W E
Department of Neurology, University of California||Kavli Institute for Fundamental Neuroscience, University of California||Weill Institute for Neuroscience, University of CaliforniaNeuroscience Program, University of California||Department of Neurology, University of California||Kavli Institute for Fundamental Neuroscience, University of California||Weill Institute for Neuroscience, University of CaliforniaNeuroscience Program, University of California||Department of Neurology, University of California||Kavli Institute for Fundamental Neuroscience, University of California||Weill Institute for Neuroscience, University of CaliforniaNeuroscience Program, University of California||Kavli Institute for Fundamental Neuroscience, University of California||Weill Institute for Neuroscience, University of CaliforniaNeuroscience Program, University of California||Kavli Institute for Fundamental Neuroscience, University of California||Weill Institute for Neuroscience, University of CaliforniaDepartment of Neurology, University of California||Kavli Institute for Fundamental Neuroscience, University of California||Weill Institute for Neuroscience, University of CaliforniaNeuroscience Program, University of California||Kavli Institute for Fundamental Neuroscience, University of California||Weill Institute for Neuroscience, University of California
神经病学、精神病学医学研究方法基础医学
Stansil Jasmine A,Bender Kevin J,Nelson Alexandra B,Schor Jonathan S,Montalvo Isabelle Gonzalez,Brakaj Rea J,Spratt Perry W E.Therapeutic Deep Brain Stimulation Disrupts Subthalamic Nucleus Activity Dynamics in Parkinsonian Mice[EB/OL].(2025-03-28)[2025-08-02].https://www.biorxiv.org/content/10.1101/2021.11.12.468404.点此复制
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