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光遗传学 fMRI 揭示了丘脑底核深部脑刺激的治疗回路。

Optogenetic fMRI reveals therapeutic circuits of subthalamic nucleus deep brain stimulation.

机构信息

Department of Biomedical Engineering, USA.

Center for Animal MRI, University of North Carolina, Chapel Hill, NC, USA; Biomedical Research Imaging Center, University of North Carolina, Chapel Hill, NC, USA; Department of Neurology, University of North Carolina, Chapel Hill, NC, USA.

出版信息

Brain Stimul. 2024 Jul-Aug;17(4):947-957. doi: 10.1016/j.brs.2024.07.022. Epub 2024 Aug 2.

DOI:10.1016/j.brs.2024.07.022
PMID:39096961
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11364984/
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.

摘要

虽然深部脑刺激 (DBS) 被广泛用于治疗帕金森病 (PD) 的运动症状，但它的确切电路机制仍存在争议。为了确定治疗性 DBS 对 PD 影响的神经靶点，我们使用功能磁共振成像 (fMRI) 分析了雌性半帕金森大鼠的 DBS 诱发全脑活动。我们使用光遗传学以不同的刺激脉冲重复率传递丘脑底核 (STN) DBS，允许对 STN 前馈神经活动的细胞类型特异性进行无偏检查。单侧光遗传学 STN DBS 诱发了 SNr（黑质网状部）、GP（苍白球）和 CPu（尾状核）中血氧水平依赖 (BOLD) 信号的脉冲重复率依赖性改变。值得注意的是，这种调制有效地改善了表达动力学更快的 Chronos 视蛋白的动物的病理性转圈行为，但对表达 ChR2 的动物没有作用。此外，中介分析表明，脉冲重复率依赖性行为挽救主要由 GP 和 CPu 中的光遗传学 DBS 诱导的活动变化介导，而不是 SNr 中的变化。这表明 GP 和 CPu 的激活在 STN DBS 的治疗机制中起着关键作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/573f/11364984/9d19e1205ecc/nihms-2018141-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/573f/11364984/226a4c12e3a8/nihms-2018141-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/573f/11364984/5f65d8ef4875/nihms-2018141-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/573f/11364984/0ef96dd99378/nihms-2018141-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/573f/11364984/eea208a10abb/nihms-2018141-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/573f/11364984/9d19e1205ecc/nihms-2018141-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/573f/11364984/226a4c12e3a8/nihms-2018141-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/573f/11364984/5f65d8ef4875/nihms-2018141-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/573f/11364984/0ef96dd99378/nihms-2018141-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/573f/11364984/eea208a10abb/nihms-2018141-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/573f/11364984/9d19e1205ecc/nihms-2018141-f0005.jpg

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