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Methods to Understand Brain Connections and Neural Function: Voltage imaging to understand connections and functions of neuronal circuits

机译:理解大脑连接和神经功能的方法:电压成像以了解神经元电路的连接和功能

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摘要

Understanding of the cellular mechanisms underlying brain functions such as cognition and emotions requires monitoring of membrane voltage at the cellular, circuit, and system levels. Seminal voltage-sensitive dye and calcium-sensitive dye imaging studies have demonstrated parallel detection of electrical activity across populations of interconnected neurons in a variety of preparations. A game-changing advance made in recent years has been the conceptualization and development of optogenetic tools, including genetically encoded indicators of voltage (GEVIs) or calcium (GECIs) and genetically encoded light-gated ion channels (actuators, e.g., channelrhodopsin2). Compared with low-molecular-weight calcium and voltage indicators (dyes), the optogenetic imaging approaches are 1) cell type specific, 2) less invasive, 3) able to relate activity and anatomy, and 4) facilitate long-term recordings of individual cells' activities over weeks, thereby allowing direct monitoring of the emergence of learned behaviors and underlying circuit mechanisms. We highlight the potential of novel approaches based on GEVIs and compare those to calcium imaging approaches. We also discuss how novel approaches based on GEVIs (and GECIs) coupled with genetically encoded actuators will promote progress in our knowledge of brain circuits and systems.
机译:要了解大脑功能(例如认知和情绪)所基于的细胞机制,需要在细胞,电路和系统水平上监测膜电压。精髓的电压敏感染料和钙敏感染料成像研究表明,在各种制剂中,互连神经元群体之间的电活动可并行检测。近年来发生的改变游戏规则的进步是光遗传学工具的概念化和开发,包括遗传编码的电压指示剂(GEVIs)或钙(GECIs)和遗传编码的光门控离子通道(执行器,例如Channelrhodopsin2)。与低分子量钙和电压指示剂(染料)相比,光遗传学成像方法是1)细胞类型特异性,2)侵入性较小,3)能够关联活动和解剖结构以及4)便于长期记录个体细胞在数周内的活动,从而可以直接监视学习到的行为和潜在的电路机制的出现。我们强调了基于GEVIs的新方法的潜力,并将其与钙成像方法进行了比较。我们还将讨论基于GEVI(和GECI)以及遗传编码的致动器的新颖方法如何促进我们对脑电路和系统的了解。

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