Forelimb movements evoked by optogenetic stimulation of the macaque motor cortex
Forelimb movements evoked by optogenetic stimulation of the macaque motor cortex
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DOI：
10.1038/s41467-020-16883-5
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发表时间：
2020-06-26
影响因子：
16.6
通讯作者：
Nambu, Atsushi
中科院分区：
文献类型：
--
作者：
Watanabe, Hidenori;Sano, Hiromi;Nambu, Atsushi
光遗传学已经成为研究大脑功能不可或缺的工具。虽然非人类灵长类动物是理解人类大脑功能和功能障碍的特别有用的模型，但光遗传学在非人类灵长类动物中的应用仍然有限。在本研究中，我们生成了一种有效的腺相关病毒载体DJ，在一种强而普遍的CAG启动子的控制下表达通道视紫质-2 (ChR2)，并将其注射到猕猴初级运动皮层的体位鉴定的前肢区域。ChR2在注射部位周围强烈表达，通过自制的光电电极进行的光遗传皮质内微刺激（oICMS）诱导了突出的皮质活动：即使是单脉冲、短时间的oICMS也会引起皮质神经元的长时间重复放电。此外，oICMS引起了不同的前肢运动和肌肉活动，这与传统的电ICMS引起的运动和肌肉活动相当。本研究消除了非人类灵长类动物神经元活动和行为的光遗传学操作障碍。非人类灵长类动物是了解人类大脑的有用模型，但将光遗传学应用于非人类灵长类动物具有挑战性。作者在猕猴初级运动皮层中使用光遗传皮层内微刺激来诱导不同的前肢运动和肌肉活动。
Optogenetics has become an indispensable tool for investigating brain functions. Although non-human primates are particularly useful models for understanding the functions and dysfunctions of the human brain, application of optogenetics to non-human primates is still limited. In the present study, we generate an effective adeno-associated viral vector serotype DJ to express channelrhodopsin-2 (ChR2) under the control of a strong ubiquitous CAG promoter and inject into the somatotopically identified forelimb region of the primary motor cortex in macaque monkeys. ChR2 is strongly expressed around the injection sites, and optogenetic intracortical microstimulation (oICMS) through a homemade optrode induces prominent cortical activity: Even single-pulse, short-duration oICMS evokes long-lasting repetitive firings of cortical neurons. In addition, oICMS elicits distinct forelimb movements and muscle activity, which are comparable to those elicited by conventional electrical ICMS. The present study removes obstacles to optogenetic manipulation of neuronal activity and behaviors in non-human primates. Non-human primates are useful models for understanding the human brain but application of optogenetics to non-human primates is challenging. The authors used optogenetic intracortical microstimulation in the primary motor cortex of macaques to elicit distinct forelimb movements and muscle activity.