[PDF][PDF] A new DREADD facilitates the multiplexed chemogenetic interrogation of behavior

E Vardy, JE Robinson, C Li, RHJ Olsen, JF DiBerto… - Neuron, 2015 - cell.com
E Vardy, JE Robinson, C Li, RHJ Olsen, JF DiBerto, PM Giguere, FM Sassano, XP Huang
Neuron, 2015cell.com
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 M 3 …
Summary
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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