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.
Digital Object Identifier (DOI)
Becnel, Jaime; Johnson, Oralee; Majeed, Zana R; Tran, Vi; Yu, Bangning; Roth, Bryan L.; Cooper, Robin L.; Kerut, Edmund K.; and Nichols, Charles D., "DREADDs in Drosophila: a Pharmacogenetic Approach for Controlling Behavior, Neuronal Signaling, and Physiology in the Fly" (2013). Biology Faculty Publications. Paper 46.