Purkinje cell misfiring generates high-amplitude action tremors that are corrected by cerebellar deep brain stimulation
Purkinje cell misfiring generates high-amplitude action tremors that are corrected by cerebellar deep brain stimulation
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DOI：
10.7554/elife.51928
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发表时间：
2020-03-17
期刊：
影响因子：
7.7
通讯作者：
Sillitoe, Roy, V
中科院分区：
文献类型：
--
作者：
Brown, Amanda M.;White, Joshua J.;Sillitoe, Roy, V
震颤目前被列为最常见的运动障碍。大脑区域和神经信号引发了身体不同部位的虚弱颤抖，目前还不清楚。在这里，我们发现基因沉默小脑浦肯野细胞输出可以阻止给予震颤药物骆驼蓬碱的小鼠的震颤。我们在清醒行为的小鼠中发现，震颤的发作与有节奏的浦肯野细胞放电一致，这改变了它们的靶小脑核细胞的活性。我们用光遗传学模拟药物的震颤作用，并提出证据表明，高度模式化的浦肯野细胞活性在其他正常小鼠中驱动强大的震颤。通过针对小脑核中浦肯野细胞输出的脑深部刺激来调节改变的活动，减少了自由活动小鼠的震颤。总之，这些数据暗示浦肯野细胞连接是震颤的神经基质和介导疾病的信号的门户。
Tremor is currently ranked as the most common movement disorder. The brain regions and neural signals that initiate the debilitating shakiness of different body parts remain unclear. Here, we found that genetically silencing cerebellar Purkinje cell output blocked tremor in mice that were given the tremorgenic drug harmaline. We show in awake behaving mice that the onset of tremor is coincident with rhythmic Purkinje cell firing, which alters the activity of their target cerebellar nuclei cells. We mimic the tremorgenic action of the drug with optogenetics and present evidence that highly patterned Purkinje cell activity drives a powerful tremor in otherwise normal mice. Modulating the altered activity with deep brain stimulation directed to the Purkinje cell output in the cerebellar nuclei reduced tremor in freely moving mice. Together, the data implicate Purkinje cell connectivity as a neural substrate for tremor and a gateway for signals that mediate the disease.