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Nature:神经回路的光开关

来源:Nature 2010-01-07 10:29

专题:Nature报道

微生物视蛋白(感光离子通道)的实验使用迎来了神经科学的一场革命,因为它们使得根据外源光调控作为遗传研究目标的神经元的活性成为可能。

现在,Ed Boyden及其同事对古细菌、细菌、植物和真菌的视蛋白新性质进行了筛选,发现了神经控制的一个全新机制:光驱动质子泵输。虽然质子原本并不是被神经系统用作载荷子,但来自Halorubrum sodomense的archaerhodopsin-3的光驱动质子泵输,能响应于光照来调控强大的神经沉默作用。来自真菌Leptosphaeria maculans的一个质子泵能够在蓝光照射下启动神经沉默。这些试剂的使用将有助于用光来关闭神经回路,作为研究神经回路在行为和病理中所起作用的一种工具。(生物谷Bioon.com)

生物谷推荐原始出处:

Nature 463, 98-102 (7 January 2010) | doi:10.1038/nature08652

High-performance genetically targetable optical neural silencing by light-driven proton pumps

Brian Y. Chow1,2,3, Xue Han1,2,3, Allison S. Dobry1,2, Xiaofeng Qian1,2, Amy S. Chuong1,2, Mingjie Li1,2, Michael A. Henninger1,2, Gabriel M. Belfort2, Yingxi Lin2, Patrick E. Monahan1,2 & Edward S. Boyden1,2

1 The MIT Media Laboratory, Synthetic Neurobiology Group, and Department of Biological Engineering,
2 Department of Brain and Cognitive Sciences and MIT McGovern Institute for Brain Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
3 These authors contributed equally to this work.

The ability to silence the activity of genetically specified neurons in a temporally precise fashion would provide the opportunity to investigate the causal role of specific cell classes in neural computations, behaviours and pathologies. Here we show that members of the class of light-driven outward proton pumps can mediate powerful, safe, multiple-colour silencing of neural activity. The gene archaerhodopsin-3 (Arch)1 from Halorubrum sodomense enables near-100% silencing of neurons in the awake brain when virally expressed in the mouse cortex and illuminated with yellow light. Arch mediates currents of several hundred picoamps at low light powers, and supports neural silencing currents approaching 900 pA at light powers easily achievable in vivo. Furthermore, Arch spontaneously recovers from light-dependent inactivation, unlike light-driven chloride pumps that enter long-lasting inactive states in response to light. These properties of Arch are appropriate to mediate the optical silencing of significant brain volumes over behaviourally relevant timescales. Arch function in neurons is well tolerated because pH excursions created by Arch illumination are minimized by self-limiting mechanisms to levels comparable to those mediated by channelrhodopsins2, 3 or natural spike firing. To highlight how proton pump ecological and genomic diversity may support new innovation, we show that the blue–green light-drivable proton pump from the fungus Leptosphaeria maculans 4 (Mac) can, when expressed in neurons, enable neural silencing by blue light, thus enabling alongside other developed reagents the potential for independent silencing of two neural populations by blue versus red light. Light-driven proton pumps thus represent a high-performance and extremely versatile class of ‘optogenetic’ voltage and ion modulator, which will broadly enable new neuroscientific, biological, neurological and psychiatric investigations.

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