Chemogenetics drives paradigm change in the investigation of behavioral circuits and neural mechanisms underlying drug action.
Chemogenetics drives paradigm change in the investigation of behavioral circuits and neural mechanisms underlying drug action.
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化学遗传学推动了药物作用下行为回路和神经机制研究的范式转变。
DOI：
10.1016/j.bbr.2021.113234
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发表时间：
2021-05-21
影响因子：
2.7
通讯作者：
Arakawa H
中科院分区：
文献类型：
--
作者：
Ozawa A;Arakawa H
研究大脑功能的化学遗传学方法的最新发展带来了药物和行为研究以及临床药物药物策略的范式变化。由于药物作用的本质是基于体液调节的，因此确定药物应用所诱导的特定靶向行为表达的神经机制是一个挑战。化学遗传学方法的发展使研究人员能够通过工具箱控制目标神经元的神经活动，包括工程G蛋白偶联受体或配体门控离子通道以及外源惰性合成配体。本文对化学遗传学工具箱进行了简要的综述，重点介绍了用于啮齿动物模型的DREADDS(由设计师药物独占激活的设计师受体)技术，该技术适用于研究特定的神经回路如何调节行为过程。化学遗传学的使用对基础神经科学产生了重大影响，使人们更好地理解大脑活动与表达具有细胞和电路特定顺序的行为之间的关系。此外，化学遗传学有可能成为解构精神疾病的神经病理机制及其药物调控的有用工具，并为我们提供药物治疗的变革性疗法。我们还回顾了利用化学遗传学技术在啮齿动物模型中揭示5-羟色胺能神经元功能回路连接的最新发现。
Recent developments in chemogenetic approaches to the investigation of brain function have ushered in a paradigm change in the strategy for drug and behavior research and clinical drug-based medications. As the nature of the drug action is based on humoral regulation, it is a challenge to identify the neuronal mechanisms responsible for the expression of certain targeted behavior induced by drug application. The development of chemogenetic approaches has allowed researchers to control neural activities in targeted neurons through a toolbox, including engineered G protein-coupled receptors or ligand-gated ion channels together with exogenously inert synthetic ligands. This review provides a brief overview of the chemogenetics toolbox with an emphasis on the DREADDs (Designer Receptors Exclusively Activated by Designer Drugs) technique used in rodent models, which is applicable to the investigation of how specific neural circuits regulate behavioral processes. The use of chemogenetics has had a significant impact on basic neuroscience for a better understanding of the relationships between brain activity and the expression of behaviors with cell- and circuit-specific orders. Furthermore, chemogenetics is potentially a useful tool to deconstruct the neuropathological mechanisms of mental diseases and its regulation by drug, and provide us with transformative therapeutics with medication. We also review recent findings in the use of chemogenetic techniques to uncover functional circuit connections of serotonergic neurons in rodent models.
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DOI：
10.1073/pnas.0700293104
发表时间：
2007-03-20
影响因子：
11.1
作者：
Armbruster, Blaine N.;Li, Xiang;Roth, Bryan L.
通讯作者：
Roth, Bryan L.
影响因子：
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影响因子：
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5
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Chen X;Choo H;Huang XP;Yang X;Stone O;Roth BL;Jin J
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影响因子：
25
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Gradinaru V