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光遗传学与药物遗传学:原理与应用

Optogenetics and pharmacogenetics: principles and applications.

作者信息

Jiang Jingwei, Cui Huxing, Rahmouni Kamal

机构信息

Department of Pharmacology, University of Iowa Carver College of Medicine, Iowa City, Iowa.

Fraternal Order of Eagles Diabetes Research Center, University of Iowa Carver College of Medicine, Iowa City, Iowa; and.

出版信息

Am J Physiol Regul Integr Comp Physiol. 2017 Dec 1;313(6):R633-R645. doi: 10.1152/ajpregu.00091.2017. Epub 2017 Aug 9.

Abstract

Remote and selective spatiotemporal control of the activity of neurons to regulate behavior and physiological functions has been a long-sought goal in system neuroscience. Identification and subsequent bioengineering of light-sensitive ion channels (e.g., channelrhodopsins, halorhodopsin, and archaerhodopsins) from the bacteria have made it possible to use light to artificially modulate neuronal activity, namely optogenetics. Recent advance in genetics has also allowed development of novel pharmacological tools to selectively and remotely control neuronal activity using engineered G protein-coupled receptors, which can be activated by otherwise inert drug-like small molecules such as the designer receptors exclusively activated by designer drug, a form of chemogenetics. The cutting-edge optogenetics and pharmacogenetics are powerful tools in neuroscience that allow selective and bidirectional modulation of the activity of defined populations of neurons with unprecedented specificity. These novel toolboxes are enabling significant advances in deciphering how the nervous system works and its influence on various physiological processes in health and disease. Here, we discuss the fundamental elements of optogenetics and chemogenetics approaches and some of the applications that yielded significant advances in various areas of neuroscience and beyond.

摘要

远程和选择性地时空控制神经元活动以调节行为和生理功能一直是系统神经科学中长期追求的目标。从细菌中鉴定并随后进行生物工程改造的光敏离子通道(如通道视紫红质、嗜盐视紫红质和古菌视紫红质)使得利用光来人工调节神经元活动成为可能,即光遗传学。遗传学的最新进展还使得开发新型药理学工具成为可能,这些工具可以利用工程化的G蛋白偶联受体选择性地远程控制神经元活动,这些受体可以被原本无活性的类药物小分子激活,如仅由设计药物激活的设计受体,这是一种化学遗传学形式。前沿的光遗传学和化学遗传学是神经科学中的强大工具,它们以前所未有的特异性允许对特定神经元群体的活动进行选择性和双向调节。这些新颖的工具箱正在推动在解读神经系统如何工作及其对健康和疾病中各种生理过程的影响方面取得重大进展。在这里,我们讨论光遗传学和化学遗传学方法的基本要素以及一些在神经科学及其他领域取得重大进展的应用。

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