A New DREADD Facilitates the Multiplexed Chemogenetic Interrogation of Behavior

Eyal Vardy, J. Elliott Robinson, Chia Li, Reid H.J. Olsen, Jeffrey F. DiBerto, Patrick M. Giguere, Flori M. Sassano, Xi Ping Huang, Hu Zhu, Daniel J. Urban, Kate L. White, Joseph E. Rittiner, Nicole A. Crowley, Kristen E. Pleil, Christopher M. Mazzone, Philip D. Mosier, Juan Song, Thomas L. Kash, C. J. Malanga, Michael J. KrashesBryan L. Roth

Research output: Contribution to journalArticlepeer-review

170 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)936-946
Number of pages11
JournalNeuron
Volume86
Issue number4
DOIs
StatePublished - May 20 2015

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

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