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. Krashes; Bryan L. Roth

doi:10.1016/j.neuron.2015.03.065

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. Krashes

Bryan L. Roth

Research output: Contribution to journal › Article › peer-review

320 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 G_i-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 G_q-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 language	English (US)
Pages (from-to)	936-946
Number of pages	11
Journal	Neuron
Volume	86
Issue number	4
DOIs	https://doi.org/10.1016/j.neuron.2015.03.065
State	Published - May 20 2015

All Science Journal Classification (ASJC) codes

General Neuroscience

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10.1016/j.neuron.2015.03.065

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Vardy, E., Robinson, J. E., Li, C., Olsen, R. H. J., DiBerto, J. F., Giguere, P. M., Sassano, F. M., Huang, X. P., Zhu, H., Urban, D. J., White, K. L., Rittiner, J. E., Crowley, N. A., Pleil, K. E., Mazzone, C. M., Mosier, P. D., Song, J., Kash, T. L., Malanga, C. J., ... Roth, B. L. (2015). A New DREADD Facilitates the Multiplexed Chemogenetic Interrogation of Behavior. Neuron, 86(4), 936-946. https://doi.org/10.1016/j.neuron.2015.03.065

@article{cd7abf3d2aa7467e98008cb2ff3ace56,

title = "A New DREADD Facilitates the Multiplexed Chemogenetic Interrogation of Behavior",

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.",

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

note = "Publisher Copyright: {\textcopyright} 2015 Elsevier Inc.",

year = "2015",

month = may,

day = "20",

doi = "10.1016/j.neuron.2015.03.065",

language = "English (US)",

volume = "86",

pages = "936--946",

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issn = "0896-6273",

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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 2015, 'A New DREADD Facilitates the Multiplexed Chemogenetic Interrogation of Behavior', Neuron, vol. 86, no. 4, pp. 936-946. https://doi.org/10.1016/j.neuron.2015.03.065

TY - JOUR

T1 - A New DREADD Facilitates the Multiplexed Chemogenetic Interrogation of Behavior

AU - Vardy, Eyal

AU - Robinson, J. Elliott

AU - Li, Chia

AU - Olsen, Reid H.J.

AU - DiBerto, Jeffrey F.

AU - Giguere, Patrick M.

AU - Sassano, Flori M.

AU - Huang, Xi Ping

AU - Zhu, Hu

AU - Urban, Daniel J.

AU - White, Kate L.

AU - Rittiner, Joseph E.

AU - Crowley, Nicole A.

AU - Pleil, Kristen E.

AU - Mazzone, Christopher M.

AU - Mosier, Philip D.

AU - Song, Juan

AU - Kash, Thomas L.

AU - Malanga, C. J.

AU - Krashes, Michael J.

AU - Roth, Bryan L.

PY - 2015/5/20

Y1 - 2015/5/20

N2 - 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.

AB - 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.

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UR - https://www.scopus.com/pages/publications/84930244375#tab=citedBy

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DO - 10.1016/j.neuron.2015.03.065

M3 - Article

C2 - 25937170

AN - SCOPUS:84930244375

SN - 0896-6273

VL - 86

SP - 936

EP - 946

JO - Neuron

JF - Neuron

IS - 4

ER -

A New DREADD Facilitates the Multiplexed Chemogenetic Interrogation of Behavior

Abstract

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