Therapeutic deep brain stimulation disrupts movement-related subthalamic nucleus activity in Parkinsonian mice
- University of California, San Francisco, United States
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 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.
Data availability
Source data can be found on Dryad, doi:10.7272/Q60P0X95.
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Data from: Therapeutic deep brain stimulation disrupts movement-related subthalamic nucleus activity in Parkinsonian miceDryad Digital Repository, doi:10.7272/dryad.Q60P0X95.
Article and author information
Author details
Alexandra B Nelson
Funding
Aligning Science Across Parkinson's (ASAP-020529)
- Alexandra B Nelson
National Institutes of Health (F31 NS110329)
- Jonathan S Schor
National Institutes of Health (K08 NS081001)
- Alexandra B Nelson
National Institutes of Health (R01NS101354)
- Alexandra B Nelson
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: This study was performed in accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All animal experiments were approved by the UC San Francisco institutional animal care and use committee (IACUC), protocol # AN189295. Efforts were made throughout to minimize the suffering of animals by use of appropriate anesthetics and analgesics, as well as enrichment and supportive care.
Copyright
© 2022, Schor et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Therapeutic deep brain stimulation disrupts movement-related subthalamic nucleus activity in Parkinsonian mice
eLife 11:e75253.
https://doi.org/10.7554/eLife.75253
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