Literature DB >> 25937170

A New DREADD Facilitates the Multiplexed Chemogenetic Interrogation of Behavior.

Eyal Vardy1, J Elliott Robinson2, Chia Li3, Reid H J Olsen4, Jeffrey F DiBerto5, Patrick M Giguere1, Flori M Sassano1, Xi-Ping Huang1, Hu Zhu1, Daniel J Urban1, Kate L White1, Joseph E Rittiner6, Nicole A Crowley7, Kristen E Pleil7, Christopher M Mazzone7, Philip D Mosier8, Juan Song4, Thomas L Kash7, C J Malanga2, Michael J Krashes9, Bryan L Roth10.   

Abstract

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.
Copyright © 2015 Elsevier Inc. All rights reserved.

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Year:  2015        PMID: 25937170      PMCID: PMC4441592          DOI: 10.1016/j.neuron.2015.03.065

Source DB:  PubMed          Journal:  Neuron        ISSN: 0896-6273            Impact factor:   17.173


  46 in total

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  147 in total

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