Department of Neurology, Yerkes National Primate Research Center, School of Medicine, Emory University, Atlanta, GA, 30329, USA.
Udall Center of Excellence for Parkinson's Disease Research, Emory University, 954 Gatewood Road NE, Atlanta, GA, 30329, USA.
J Neural Transm (Vienna). 2018 Mar;125(3):547-563. doi: 10.1007/s00702-017-1697-8. Epub 2017 Feb 25.
Over the last 10 years, the use of opto- and chemogenetics to modulate neuronal activity in research applications has increased exponentially. Both techniques involve the genetic delivery of artificial proteins (opsins or engineered receptors) that are expressed on a selective population of neurons. The firing of these neurons can then be manipulated using light sources (for opsins) or by systemic administration of exogenous compounds (for chemogenetic receptors). Opto- and chemogenetic tools have enabled many important advances in basal ganglia research in rodent models, yet these techniques have faced a slow progress in non-human primate (NHP) research. In this review, we present a summary of the current state of these techniques in NHP research and outline some of the main challenges associated with the use of these genetic-based approaches in monkeys. We also explore cutting-edge developments that will facilitate the use of opto- and chemogenetics in NHPs, and help advance our understanding of basal ganglia circuits in normal and pathological conditions.
在过去的 10 年中，利用光学遗传学和化学遗传学来调节神经元活性的研究应用呈指数级增长。这两种技术都涉及到人工蛋白质（视蛋白或工程受体）的基因传递，这些蛋白质在选择性神经元群体上表达。然后可以使用光源（用于视蛋白）或通过系统给予外源性化合物（用于化学遗传学受体）来操纵这些神经元的发射。光学遗传学和化学遗传学工具在啮齿动物模型的基底神经节研究中取得了许多重要进展，但这些技术在非人类灵长类动物（NHP）研究中进展缓慢。在这篇综述中，我们总结了这些技术在 NHP 研究中的现状，并概述了在猴子中使用这些基于遗传的方法所涉及的一些主要挑战。我们还探讨了一些前沿的发展，这些发展将有助于在 NHP 中使用光学遗传学和化学遗传学，并有助于加深我们对正常和病理条件下基底神经节回路的理解。
