Neuron:成体脑细胞基因编辑调控个体运动

Selective Optogenetic Control of Purkinje Cells in Monkey Cerebellum

来自华盛顿大学医学院的研究者们最近开发出了一种新的技术。能够将基因转入成体大脑的特定细胞中。这一技术已经在动物水平上得到了验证。最近的这一研究结果表明，该技术能够用于改变脑回路的功能，并改变动物的行为，相关结果发表在《Neuron》杂志上。

Purkinje cells of the primate cerebellum play critical but poorly understood roles in the execution of coordinated, accurate movements. Elucidating these roles has been hampered by a lack of techniques for manipulating spiking activity in these cells selectively—a problem common to most cell types in non-transgenic animals. To overcome this obstacle, we constructed AAV vectors carrying the channelrhodopsin-2 (ChR2) gene under the control of a 1 kb L7/Pcp2 promoter. We injected these vectors into the cerebellar cortex of rhesus macaques and tested vector efficacy in three ways. Immunohistochemical analyses confirmed selective ChR2 expression in Purkinje cells. Neurophysiological recordings confirmed robust optogenetic activation. Optical stimulation of the oculomotor vermis caused saccade dysmetria. Our results demonstrate the utility of AAV-L7-ChR2 for revealing the contributions of Purkinje cells to circuit function and behavior, and they attest to the feasibility of promoter-based, targeted, genetic manipulations in primates.