A viral strategy for targeting and manipulating interneurons across vertebrate species.
A viral strategy for targeting and manipulating interneurons across vertebrate species.
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DOI：
10.1038/nn.4430
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发表时间：
2016-12
影响因子：
25
通讯作者：
Fishell G
中科院分区：
文献类型：
--
作者：
Dimidschstein J;Chen Q;Tremblay R;Rogers SL;Saldi GA;Guo L;Xu Q;Liu R;Lu C;Chu J;Grimley JS;Krostag AR;Kaykas A;Avery MC;Rashid MS;Baek M;Jacob AL;Smith GB;Wilson DE;Kosche G;Kruglikov I;Rusielewicz T;Kotak VC;Mowery TM;Anderson SA;Callaway EM;Dasen JS;Fitzpatrick D;Fossati V;Long MA;Noggle S;Reynolds JH;Sanes DH;Rudy B;Feng G;Fishell G
理解大脑的一个根本障碍是针对和操纵特定神经元群体的廉价而强大的方法的可用性。克服这一障碍的需要是紧迫的，因为小鼠和高等哺乳动物物种之间存在相当大的解剖学，生理学，认知和行为差异，难以特异性靶向和操纵遗传定义的功能细胞类型。特别是，目前尚不清楚小鼠模型的见解在多大程度上可以揭示介导包括人类在内的高等物种认知功能的神经机制。在这里，我们描述了一种新的重组腺相关病毒（rAAV），限制端脑内的GABA能中间神经元的基因表达。我们证明，病毒表达是具体的和强大的，允许形态可视化，活动监测和功能操作的interneurons在小鼠和非遗传听话的物种，从而打开的可能性，研究GABA能功能在几乎任何脊椎动物物种。
A fundamental impediment to understanding the brain is the availability of inexpensive and robust methods for targeting and manipulating specific neuronal populations. The need to overcome this barrier is pressing because there are considerable anatomical, physiological, cognitive, and behavioral differences between mice and higher mammalian species in which it is difficult to specifically target and manipulate genetically defined functional cell-types. In particular, it is unclear the degree to which insights from mouse models can shed light on the neural mechanisms that mediate cognitive functions in higher species including humans. Here we describe a novel recombinant adeno-associated virus (rAAV) that restricts gene expression to GABAergic interneurons within the telencephalon. We demonstrate that the viral expression is specific and robust, allowing for morphological visualization, activity monitoring and functional manipulation of interneurons in both mice and non-genetically tractable species, thus opening the possibility to study GABA-ergic function in virtually any vertebrate species.