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Selective activation of subthalamic nucleus output quantitatively scales movements

Alexander D. Friedman, Henry H. Yin
doi: https://doi.org/10.1101/2022.01.19.477002
Alexander D. Friedman
1Department of Psychology and Neuroscience; Duke University; Durham, NC, 27708; USA
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Henry H. Yin
1Department of Psychology and Neuroscience; Duke University; Durham, NC, 27708; USA
2Department of Neurobiology; Duke University School of Medicine; Durham, NC, 27708; USA
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  • For correspondence: hy43@duke.edu
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Abstract

The subthalamic nucleus (STN), a diencephalic nucleus strongly connected with the basal ganglia, is a common target for deep brain stimulation (DBS) treatments of Parkinsonian motor symptoms. The STN is thought to suppress movement by enhancing inhibitory basal ganglia output via the indirect pathway, and disrupting STN output using DBS can restore movement in Parkinson’s patients. However, previous studies on STN DBS usually relied on electrical stimulation, which cannot selectively target STN output neurons. Moreover, most studies did not measure behavior precisely during STN manipulations. Here we selectively stimulated STN projection neurons, by expressing channelrhodopsin in vesicular glutamate transporter 2 (VGlut2)-positive projection neurons in the STN. We also quantified behavior in freely moving male mice with high spatial and temporal resolution using 3D motion capture at 200 frames per second. We found STN stimulation resulted in movements with very short latencies (10-15 ms). Unilateral stimulation quantitatively determines orientation, head yaw, and head roll consistently in the ipsiversive direction, toward thee side of stimulation. On the other hand, head raising (increased head pitch) was observed after stimulation on either side. Strikingly, a single pulse of light was sufficient to generate movement, and there was a highly linear relationship between stimulation frequency and kinematics. These results question the common assumption that STN suppresses movement; instead they suggest that STN output can precisely specific action parameters via direct projections to brainstem regions.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • Conflict of interest: The authors declare no competing financial interests.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted January 22, 2022.
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Selective activation of subthalamic nucleus output quantitatively scales movements
Alexander D. Friedman, Henry H. Yin
bioRxiv 2022.01.19.477002; doi: https://doi.org/10.1101/2022.01.19.477002
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Selective activation of subthalamic nucleus output quantitatively scales movements
Alexander D. Friedman, Henry H. Yin
bioRxiv 2022.01.19.477002; doi: https://doi.org/10.1101/2022.01.19.477002

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