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
中科院分区:
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
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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