Mouse transgenic approaches in optogenetics.
Mouse transgenic approaches in optogenetics.
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DOI：
10.1016/b978-0-444-59426-6.00010-0
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发表时间：
2012
影响因子：
--
通讯作者：
Madisen, Linda
中科院分区：
文献类型：
--
作者：
Zeng, Hongkui;Madisen, Linda
关键词：
神经科学的一个主要挑战是了解普遍的行为，如感觉、运动、认知和情感，是如何由大脑中复杂的神经网络内存在的特定细胞的相互作用产生的。对此类复杂网络的剖析通常依赖于扰乱单个基因产物的活性，扰乱神经元的药理学活动，或损害特定的大脑区域，以研究网络在行为输出中的反应。尽管这些方法为多种研究提供了丰富的信息，但这些方法还不足以在空间或时间限制的背景下检查特定细胞或细胞类别的功能。光遗传学领域的最新进展现在使研究人员能够以光独特的速度和精度监测和操纵基因定义的细胞群的活动。转基因小鼠以细胞类型特异性方式表达光遗传学工具，为以明确且可重复的方式检查特定细胞在离散电路中的作用提供了一种强大的方法。因此，毫不奇怪，近年来人们为产生表达功能相关水平的光遗传学工具的转基因小鼠品系付出了巨大的努力。在本章中，我们回顾了这些努力的现状，并考虑了当前技术中可以从进一步改进中受益的方面。
A major challenge in neuroscience is to understand how universal behaviors, such as sensation, movement, cognition, and emotion, arise from the interactions of specific cells that are present within intricate neural networks in the brain. Dissection of such complex networks has typically relied on disturbing the activity of individual gene products, perturbing neuronal activities pharmacologically, or lesioning specific brain regions, to investigate the network’s response in a behavioral output. Though informative for many kinds of studies, these approaches are not sufficiently fine-tuned for examining the functionality of specific cells or cell classes in a spatially or temporally-restricted context. Recent advances in the field of optogenetics now enable researchers to monitor and manipulate the activity of genetically defined cell populations with the speed and precision uniquely afforded by light. Transgenic mice engineered to express optogenetic tools in a cell type-specific manner offer a powerful approach for examining the role of particular cells in discrete circuits in a defined and reproducible way. Not surprisingly then, recent years have seen substantial efforts directed towards generating transgenic mouse lines that express functionally relevant levels of optogenetic tools. In this chapter, we review the state of these efforts and consider aspects of the current technology that would benefit from additional improvement.