DREADDs in Drosophila: A Pharmacogenetic Approach for Controlling Behavior, Neuronal Signaling, and Physiology in the Fly
Jaime Becnel,
Oralee Johnson,
Zana R. Majeed,
Vi Tran,
Bangning Yu,
Bryan L. Roth,
Robin L. Cooper,
Edmund K. Kerut,
Charles D. Nichols
Affiliations
Jaime Becnel
Department of Pharmacology and Experimental Therapeutics, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA
Oralee Johnson
Department of Pharmacology and Experimental Therapeutics, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA
Zana R. Majeed
Department of Biology, University of Kentucky, Lexington, KY 40506, USA
Vi Tran
Department of Pharmacology and Experimental Therapeutics, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA
Bangning Yu
Department of Pharmacology and Experimental Therapeutics, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA
Bryan L. Roth
Department of Pharmacology and Division of Chemical Biology and Medicinal Chemistry, University of North Carolina Medical School, Chapel Hill, NC 27599, USA
Robin L. Cooper
Department of Biology, University of Kentucky, Lexington, KY 40506, USA
Edmund K. Kerut
Department of Cardiopulmonary Science, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA
Charles D. Nichols
Department of Pharmacology and Experimental Therapeutics, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA
We have translated a powerful genetic tool, designer receptors exclusively activated by designer drugs (DREADDs), from mammalian systems to Drosophila melanogaster to selectively, rapidly, reversibly, and dose-dependently control behaviors and physiological processes in the fly. DREADDs are muscarinic acetylcholine G protein-coupled receptors evolved for loss of affinity to acetylcholine and for the ability to be fully activated by an otherwise biologically inert chemical, clozapine-N-oxide. We demonstrate its ability to control a variety of behaviors and processes in larvae and adults, including heart rate, sensory processing, diurnal behavior, learning and memory, and courtship. The advantages of this particular technology include the dose-responsive control of behaviors, the lack of a need for specialized equipment, and the capacity to remotely control signaling in essentially all neuronal and nonneuronal fly tissues.
