Zhang Feng, Wang Li-Ping, Brauner Martin, Liewald Jana F, Kay Kenneth, Watzke Natalie, Wood Phillip G, Bamberg Ernst, Nagel Georg, Gottschalk Alexander, Deisseroth Karl
Department of Bioengineering, Stanford University, Stanford, California 94305, USA.
Nature. 2007 Apr 5;446(7136):633-9. doi: 10.1038/nature05744.
Our understanding of the cellular implementation of systems-level neural processes like action, thought and emotion has been limited by the availability of tools to interrogate specific classes of neural cells within intact, living brain tissue. Here we identify and develop an archaeal light-driven chloride pump (NpHR) from Natronomonas pharaonis for temporally precise optical inhibition of neural activity. NpHR allows either knockout of single action potentials, or sustained blockade of spiking. NpHR is compatible with ChR2, the previous optical excitation technology we have described, in that the two opposing probes operate at similar light powers but with well-separated action spectra. NpHR, like ChR2, functions in mammals without exogenous cofactors, and the two probes can be integrated with calcium imaging in mammalian brain tissue for bidirectional optical modulation and readout of neural activity. Likewise, NpHR and ChR2 can be targeted together to Caenorhabditis elegans muscle and cholinergic motor neurons to control locomotion bidirectionally. NpHR and ChR2 form a complete system for multimodal, high-speed, genetically targeted, all-optical interrogation of living neural circuits.
我们对诸如行动、思维和情感等系统级神经过程的细胞层面实现的理解，一直受到在完整的活体脑组织中研究特定类型神经细胞的工具的限制。在此，我们从嗜盐栖热菌中鉴定并开发了一种古菌光驱动氯离子泵（NpHR），用于对神经活动进行时间精确的光抑制。NpHR能够消除单个动作电位，或持续阻断放电。NpHR与我们之前描述的光激发技术ChR2兼容，这两种相反的探针在相似的光功率下工作，但具有分开的作用光谱。NpHR与ChR2一样，在哺乳动物中无需外源性辅助因子即可发挥作用，并且这两种探针可与哺乳动物脑组织中的钙成像整合，用于对神经活动进行双向光调制和读出。同样，NpHR和ChR2可以共同靶向秀丽隐杆线虫的肌肉和胆碱能运动神经元，以双向控制运动。NpHR和ChR2形成了一个完整的系统，用于对活体神经回路进行多模态、高速、基因靶向的全光探测。
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