1. Optogenetic fMRI reveals therapeutic circuits of subthalamic nucleus deep brain stimulation.
- Author
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Li Y, Lee SH, Yu C, Hsu LM, Wang TW, Do K, Kim HJ, Shih YI, and Grill WM
- Subjects
- Animals, Female, Rats, Rats, Sprague-Dawley, Parkinson Disease therapy, Parkinson Disease physiopathology, Parkinson Disease diagnostic imaging, Globus Pallidus physiology, Globus Pallidus diagnostic imaging, Deep Brain Stimulation methods, Subthalamic Nucleus physiology, Subthalamic Nucleus diagnostic imaging, Optogenetics methods, Magnetic Resonance Imaging
- Abstract
While deep brain stimulation (DBS) is widely employed for managing motor symptoms in Parkinson's disease (PD), its exact circuit mechanisms remain controversial. To identify the neural targets affected by therapeutic DBS in PD, we analyzed DBS-evoked whole brain activity in female hemi-parkinsonian rats using functional magnetic resonance imaging (fMRI). We delivered subthalamic nucleus (STN) DBS at various stimulation pulse repetition rates using optogenetics, allowing unbiased examination of cell-type specific STN feedforward neural activity. Unilateral optogenetic STN DBS elicited pulse repetition rate-dependent alterations of blood-oxygenation-level-dependent (BOLD) signals in SNr (substantia nigra pars reticulata), GP (globus pallidus), and CPu (caudate putamen). Notably, this modulation effectively ameliorated pathological circling behavior in animals expressing the kinetically faster Chronos opsin, but not in animals expressing ChR2. Furthermore, mediation analysis revealed that the pulse repetition rate-dependent behavioral rescue was significantly mediated by optogenetic DBS induced activity changes in GP and CPu, but not in SNr. This suggests that the activation of GP and CPu are critically involved in the therapeutic mechanisms of STN DBS., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2024
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