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A New DREADD Facilitates the Multiplexed Chemogenetic Interrogation of Behavior
Eyal Vardy1, J Elliott Robinson2, Chia Li3
1Department of Pharmacology and National Institute of Mental Health Psychoactive Drug Screening Program (NIMH PDSP), University of North Carolina School of Medicine, Chapel Hill, NC 27514, USA.
Neuron
|May 5, 2015
Summary
Researchers developed a novel chemogenetic tool, kappa-opioid receptor-derived DREADD (KORD), activated by salvinorin B. This tool enables remote control of neuronal activity and behavior, offering new possibilities for physiological research.
Area of Science:
- Neuroscience
- Pharmacology
- Molecular Biology
Background:
- Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) are crucial for remote control of cellular functions.
- Existing DREADDs have limitations in specificity and multiplexing capabilities.
Purpose of the Study:
- To develop a novel Gi-coupled DREADD using a structure-based approach.
- To enable remote, bidirectional control of neuronal activity and behavior using distinct DREADD systems.
Main Methods:
- Utilized a structure-based approach to engineer a new DREADD based on the kappa-opioid receptor (KORD).
- Employed viral expression systems to deliver KORD into various neuronal populations.
- Administered salvinorin B (SALB) as the specific activator for KORD.
- Investigated KORD function in neuronal activity and behavioral modification.
- Examined the co-expression of KORD with a Gq-coupled M3-DREADD for sequential control.
Main Results:
- Successfully developed and validated KORD, a Gi-coupled DREADD activated by SALB.
- Demonstrated robust attenuation of neuronal activity and modification of behaviors upon KORD activation.
- Showcased sequential and bidirectional remote control of behavior through co-expression of KORD and M3-DREADD.
Conclusions:
- The novel KORD provides a new chemogenetic tool for precise neuronal control.
- Multiplexed DREADD systems offer enhanced capabilities for complex physiological investigations.
- This advancement expands the toolkit for studying diverse biological systems with chemogenetics.
