A New DREADD Facilitates the Multiplexed Chemogenetic Interrogation of Behavior.

A New DREADD Facilitates the Multiplexed Chemogenetic Interrogation of Behavior.
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DOI:
10.1016/j.neuron.2015.03.065
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发表时间:
2015-05-20
期刊:
影响因子:
16.2
通讯作者:
Roth BL
Roth BL
中科院分区:
医学1区
文献类型:
--
作者:
Vardy E;Robinson JE;Li C;Olsen RHJ;DiBerto JF;Giguere PM;Sassano FM;Huang XP;Zhu H;Urban DJ;White KL;Rittiner JE;Crowley NA;Pleil KE;Mazzone CM;Mosier PD;Song J;Kash TL;Malanga CJ;Krashes MJ;Roth BL

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DREADD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学工具。在这里,我们使用基于结构的方法来开发新的Gi偶联的DREADD,其使用κ-阿片样物质受体作为模板(KORD),所述KORD由非生物活性配体鼠尾草素B(SALB)激活。病毒表达的KORD在几种神经元环境中的激活强烈地减弱了神经元活动和改变的行为。此外,KORD和Gq偶联的M3-DREADD在同一神经元群体内的共表达促进了行为的顺序和双向远程控制。由不同配体激活的DREADD的可用性为使用多重化学遗传致动器研究不同的生理系统提供了增强的机会。
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 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 bi-directional remote control of behavior. The availability of DREADDs activated by different ligands provides enhanced opportunities for investigating diverse physiological systems using multiplexed chemogenetic actuators.
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