PT  - JOURNAL ARTICLE
AU  - Jonathan S Schor
AU  - Isabelle Gonzalez Montalvo
AU  - Perry W E Spratt
AU  - Rea J Brakaj
AU  - Jasmine A Stansil
AU  - Kevin J Bender
AU  - Alexandra B Nelson
TI  - Therapeutic Deep Brain Stimulation Disrupts Subthalamic Nucleus Activity Dynamics in Parkinsonian Mice
AID  - 10.1101/2021.11.12.468404
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.11.12.468404
4099  - http://biorxiv.org/content/early/2021/11/13/2021.11.12.468404.short
4100  - http://biorxiv.org/content/early/2021/11/13/2021.11.12.468404.full
AB  - 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.Competing Interest StatementThe authors have declared no competing interest.