Genetically encoded molecular tools for light-driven silencing of targeted neurons.
Genetically encoded molecular tools for light-driven silencing of targeted neurons.
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DOI：
10.1016/b978-0-444-59426-6.00003-3
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发表时间：
2012
影响因子：
--
通讯作者：
Boyden, Edward S.
中科院分区：
文献类型：
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作者：
Chow, Brian Y.;Han, Xue;Boyden, Edward S.
关键词：
以一种暂时精确的方式使完整脑组织内特定神经元的电活动沉默的能力，对于理解这些神经元在行为、大脑紊乱和神经计算中所起的作用非常重要。“光遗传”消声器是一种基因编码分子，当它在神经网络中的目标细胞中表达时，可以使它们的电活动对光脉冲做出反应，从而使这些因果电路分析研究成为可能。两种主要的光遗传消音剂广泛应用于从蠕虫到猴子的物种：一种是向内驱动的氯离子泵，或称为盐紫红质；另一种是向外驱动的质子泵，如古紫红质和真菌光驱动质子泵。这两类分子，当通过病毒或其他转基因手段在神经元中表达时，使目标神经元被光超极化。我们在这里回顾了这些分子的现状，并讨论了它们是如何被发现和改造的。我们还讨论了它们的表达特性、离子特性、光谱特性和动力学。这些工具不仅可以在基础科学研究中找到许多安静的电活动的用途，而且还可以在未来找到临床用途，因为它们能够以精确的方式安全、短暂地关闭细胞电活动。
The ability to silence, in a temporally precise fashion, the electrical activity of specific neurons embedded within intact brain tissue, is important for understanding the role that those neurons play in behaviors, brain disorders, and neural computations. “Optogenetic” silencers, genetically encoded molecules that, when expressed in targeted cells within neural networks, enable their electrical activity to be quieted in response to pulses of light, are enabling these kinds of causal circuit analyses studies. Two major classes of optogenetic silencer are in broad use in species ranging from worm to monkey: light-driven inward chloride pumps, or halorhodopsins, and light-driven outward proton pumps, such as archaerhodopsins and fungal light-driven proton pumps. Both classes of molecule, when expressed in neurons via viral or other transgenic means, enable the targeted neurons to be hyperpolarized by light. We here review the current status of these sets of molecules, and discuss how they are being discovered and engineered. We also discuss their expression properties, ionic properties, spectral characteristics, and kinetics. Such tools may not only find many uses in the quieting of electrical activity for basic science studies, but may also, in the future, find clinical uses for their ability to safely and transiently shut down cellular electrical activity in a precise fashion.