Establishing causality for dopamine in neural function and behavior with optogenetics.
Establishing causality for dopamine in neural function and behavior with optogenetics.
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DOI：
10.1016/j.brainres.2012.09.036
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发表时间：
2013-05-20
期刊：
影响因子：
2.9
通讯作者：
Janak PH
中科院分区：
文献类型：
--
作者：
Steinberg EE;Janak PH
多巴胺（DA）在神经功能和行为中起重要作用。因此，DA神经元一直是密集的实验研究的焦点，这导致了我们对DA如何影响这些过程的理解的许多重要进展。然而，人们越来越认识到，描绘DA神经元的细胞，电路和系统级的现象的精确贡献将需要更复杂的控制其活动模式比传统技术可以提供。具体而言，DA神经元所扮演的角色可能取决于它们的传入和传出连接，它们的神经激活的时间和长度，以及正在研究的行为的性质。最近开发的光遗传学工具为解开这些复杂问题带来了巨大的希望。在这里，我们讨论了使用光敏微生物视蛋白在DA研究中的突出问题的背景下。这些蛋白质提供的一个主要技术进步是能够在体外和体内制剂中双向调节DA神经元活性，其时间尺度更接近神经，感知和行为事件。此外，啮齿动物遗传学和病毒介导的基因传递的持续进展有助于选择性靶向DA神经元或其个体传入和传出连接的能力。此外，这些工具适用于从事复杂行为的实验对象。在回顾了光遗传学方法的优势和局限性后，我们总结了这种有价值的新方法的早期应用，证明了它有潜力提高我们对DA的神经和行为功能的理解。
Dopamine (DA) is known to play essential roles in neural function and behavior. Accordingly, DA neurons have been the focus of intense experimental investigation that has led to many important advances in our understanding of how DA influences these processes. However, it is becoming increasingly appreciated that delineating the precise contributions of DA neurons to cellular, circuit, and systems-level phenomena will require more sophisticated control over their patterns of activity than conventional techniques can provide. Specifically, the roles played by DA neurons are likely to depend on their afferent and efferent connectivity, the timing and length of their neural activation, and the nature of the behavior under investigation. Recently developed optogenetic tools hold great promise for disentangling these complex issues. Here we discuss the use of light-sensitive microbial opsins in the context of outstanding questions in DA research. A major technical advance offered by these proteins is the ability to bidirectionally modulate DA neuron activity in in vitro and in vivo preparations on a time scale that more closely approximates those of neural, perceptual and behavioral events. In addition, continued advances in rodent genetics and viral-mediated gene delivery have contributed to the ability to selectively target DA neurons or their individual afferent and efferent connections. Further, these tools are suitable for use in experimental subjects engaged in complex behaviors. After reviewing the strengths and limitations of optogenetic methodologies, we conclude by describing early efforts in the application of this valuable new approach that demonstrate its potential to improve our understanding of the neural and behavioral functions of DA.
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