Vardy Eyal, Robinson J Elliott, Li Chia, Olsen Reid H J, DiBerto Jeffrey F, Giguere Patrick M, Sassano Flori M, Huang Xi-Ping, Zhu Hu, Urban Daniel J, White Kate L, Rittiner Joseph E, Crowley Nicole A, Pleil Kristen E, Mazzone Christopher M, Mosier Philip D, Song Juan, Kash Thomas L, Malanga C J, Krashes Michael J, Roth Bryan L
Department of Pharmacology and National Institute of Mental Health Psychoactive Drug Screening Program (NIMH PDSP), University of North Carolina School of Medicine, Chapel Hill, NC 27514, USA.
Neurology Department, University of North Carolina School of Medicine, Chapel Hill, NC 27514, USA; Curriculum in Neurobiology, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA; Bowles Center for Alcohol Studies, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA.
Neuron. 2015 May 20;86(4):936-946. doi: 10.1016/j.neuron.2015.03.065. Epub 2015 Apr 30.
DREADDs are chemogenetic tools widely used to remotely control cellular signaling, neuronal activity, and behavior. Here we used a structure-based approach to develop a new Gi-coupled DREADD using the kappa-opioid receptor as a template (KORD) that is activated by the pharmacologically inert ligand salvinorin B (SALB). Activation of virally expressed KORD in several neuronal contexts robustly attenuated neuronal activity and modified behaviors. Additionally, co-expression of the KORD and the Gq-coupled M3-DREADD within the same neuronal population facilitated the sequential and bidirectional remote control of behavior. The availability of DREADDs activated by different ligands provides enhanced opportunities for investigating diverse physiological systems using multiplexed chemogenetic actuators.
设计药物激活的设计受体专门激活的设计药物（DREADDs）是广泛用于远程控制细胞信号传导、神经元活动和行为的化学遗传工具。在这里，我们采用基于结构的方法，以κ-阿片受体为模板开发了一种新的Gi偶联DREADD（KORD），它可被药理惰性配体Salvinorin B（SALB）激活。在几种神经元环境中病毒表达的KORD的激活强烈减弱了神经元活动并改变了行为。此外，在同一神经元群体中共表达KORD和Gq偶联的M3-DREADD有助于对行为进行顺序和双向远程控制。由不同配体激活的DREADDs的可用性为使用多重化学遗传致动器研究各种生理系统提供了更多机会。
