Berlin Shai, Isacoff Ehud Y
The Ruth and Bruce Rappaport Faculty of Medicine, Technion- Israel Institute of Technology, Haifa, Israel
Helen Wills Neuroscience Institute, University of California, Berkeley, CA, USA.
EMBO Rep. 2017 May;18(5):677-692. doi: 10.15252/embr.201744010. Epub 2017 Apr 10.
Membrane receptors and ion channels respond to various stimuli and relay that information across the plasma membrane by triggering specific and timed processes. These include activation of second messengers, allowing ion permeation, and changing cellular excitability, to name a few. Gaining control over equivalent processes is essential to understand neuronal physiology and pathophysiology. Recently, new optical techniques have emerged proffering new remote means to control various functions of defined neuronal populations by light, dubbed optogenetics. Still, optogenetic tools do not typically address the activity of receptors and channels native to neurons (or of neuronal origin), nor gain access to their signaling mechanisms. A related method-synthetic optogenetics-bridges this gap by endowing light sensitivity to endogenous neuronal receptors and channels by the appending of synthetic, light-receptive molecules, or photoswitches. This provides the means to photoregulate neuronal receptors and channels and tap into their native signaling mechanisms in select regions of the neurons, such as the synapse. This review discusses the development of synthetic optogenetics as a means to study neuronal receptors and channels remotely, in their natural environment, with unprecedented spatial and temporal precision, and provides an overview of tool design, mode of action, potential clinical applications and insights and achievements gained.
膜受体和离子通道对各种刺激做出反应，并通过触发特定的定时过程将信息传递过质膜。这些过程包括激活第二信使、允许离子通透以及改变细胞兴奋性等。控制这些等效过程对于理解神经元生理学和病理生理学至关重要。最近，出现了新的光学技术，提供了通过光控制特定神经元群体各种功能的新远程手段，即光遗传学。然而，光遗传学工具通常无法解决神经元（或神经元起源的）天然受体和通道的活性问题，也无法了解其信号传导机制。一种相关方法——合成光遗传学——通过附加合成的光感受分子或光开关，赋予内源性神经元受体和通道光敏感性，从而弥补了这一差距。这提供了光调节神经元受体和通道并深入了解其在神经元特定区域（如突触）的天然信号传导机制的手段。本综述讨论了合成光遗传学作为一种在自然环境中以前所未有的空间和时间精度远程研究神经元受体和通道的手段的发展，并概述了工具设计、作用方式、潜在临床应用以及所获得的见解和成就。
