微生物視蛋白(感光離子通道)的實(shí)驗(yàn)使用迎來了神經(jīng)科學(xué)的一場(chǎng)革命,,因?yàn)樗鼈兪沟酶鶕?jù)外源光調(diào)控作為遺傳研究目標(biāo)的神經(jīng)元的活性成為可能,。
現(xiàn)在,,Ed Boyden及其同事對(duì)古細(xì)菌、細(xì)菌,、植物和真菌的視蛋白新性質(zhì)進(jìn)行了篩選,,發(fā)現(xiàn)了神經(jīng)控制的一個(gè)全新機(jī)制:光驅(qū)動(dòng)質(zhì)子泵輸。雖然質(zhì)子原本并不是被神經(jīng)系統(tǒng)用作載荷子,但來自Halorubrum sodomense的archaerhodopsin-3的光驅(qū)動(dòng)質(zhì)子泵輸,,能響應(yīng)于光照來調(diào)控強(qiáng)大的神經(jīng)沉默作用,。來自真菌Leptosphaeria maculans的一個(gè)質(zhì)子泵能夠在藍(lán)光照射下啟動(dòng)神經(jīng)沉默。這些試劑的使用將有助于用光來關(guān)閉神經(jīng)回路,,作為研究神經(jīng)回路在行為和病理中所起作用的一種工具,。(生物谷Bioon.com)
生物谷推薦原始出處:
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.