Therapeutic deep brain stimulation disrupts movement-related subthalamic nucleus activity in parkinsonian mice.
Therapeutic deep brain stimulation disrupts movement-related subthalamic nucleus activity in parkinsonian mice.
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DOI：
10.7554/elife.75253
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发表时间：
2022-07-04
期刊：
影响因子：
7.7
通讯作者：
Nelson, Alexandra B.
中科院分区：
文献类型：
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作者：
Schor, Jonathan S.;Montalvo, Isabelle Gonzalez;Spratt, Perry W. E.;Brakaj, Rea J.;Stansil, Jasmine A.;Twedell, Emily L.;Bender, Kevin J.;Nelson, Alexandra B.
关键词：
丘脑底核脑深部电刺激（Subthalamic nucleus deep brain stimulation，DBS）可缓解帕金森病（Parkinson's disease，PD）的许多运动症状，但其治疗机制尚不清楚。自其出现以来，已经提出了三个主要理论：（1）DBS抑制丘脑和基底神经节输出;（2）DBS逆向激活运动皮层;（3）DBS破坏丘脑内的放电动力学。以前，刺激相关的电伪影限制了使用电生理学的机械研究。我们使用无电伪影GCaMP纤维光度法研究帕金森病小鼠在DBS期间基底节核的活动。为了测试所观察到的活动变化是否足以缓解运动症状，我们将电生理记录与靶向光学DBS协议相结合。我们的研究结果表明，DBS是通过破坏运动相关的神经活动来发挥其治疗作用的，而不是抑制或逆向激活。这些结果为优化PD治疗提供了见解，并建立了在其他神经精神疾病中研究DBS的方法。
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.