Optogenetic manipulation of neural and non‐neural functions
Optogenetic manipulation of neural and non‐neural functions
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DOI：
10.1111/dgd.12053
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发表时间：
2013-05
期刊：
影响因子：
4.6
通讯作者：
H. Yawo;T. Asano;Seiichiro Sakai;T. Ishizuka
中科院分区：
文献类型：
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作者：
H. Yawo;T. Asano;Seiichiro Sakai;T. Ishizuka
神经元活动的光遗传学操纵使人们能够以精确的时空分辨率分析体内和体外的神经元网络。嗜盐视紫红质（ChR）是光敏阳离子通道，可降解细胞膜，而盐视紫红质和古视紫红质分别是光敏Cl−和H+转运蛋白，当外源表达时会过度增殖。因此，神经元及其在大脑中的功能之间的因果关系被双向研究，并有必要性和充分性的证据。在这篇综述中，我们讨论了光遗传学的潜力，重点是其应用的三个主要要求：（i）选择最适合光遗传学研究的光敏蛋白质，（ii）在特定神经元组中靶向表达这些选定的蛋白质，以及（iii）具有高时空分辨率的靶向照射。我们还讨论了光遗传学应用于非神经细胞研究的最新进展，如神经胶质细胞，心肌细胞和骨骼肌细胞。与干细胞技术相结合，光遗传学可能是使用胚胎干细胞（ESC）和诱导多能干细胞（iPSC）成功研究的关键，这些细胞来自人类患者，通过光学调节分化成熟，通过光学操作组织移植物，此外，通过促进移植物的存活和整合。
Optogenetic manipulation of the neuronal activity enables one to analyze the neuronal network both in vivo and in vitro with precise spatio‐temporal resolution. Channelrhodopsins (ChRs) are light‐sensitive cation channels that depolarize the cell membrane, whereas halorhodopsins and archaerhodopsins are light‐sensitive Cl− and H+ transporters, respectively, that hyperpolarize it when exogenously expressed. The cause‐effect relationship between a neuron and its function in the brain is thus bi‐directionally investigated with evidence of necessity and sufficiency. In this review we discuss the potential of optogenetics with a focus on three major requirements for its application: (i) selection of the light‐sensitive proteins optimal for optogenetic investigation, (ii) targeted expression of these selected proteins in a specific group of neurons, and (iii) targeted irradiation with high spatiotemporal resolution. We also discuss recent progress in the application of optogenetics to studies of non‐neural cells such as glial cells, cardiac and skeletal myocytes. In combination with stem cell technology, optogenetics may be key to successful research using embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) derived from human patients through optical regulation of differentiation‐maturation, through optical manipulation of tissue transplants and, furthermore, through facilitating survival and integration of transplants.