title: DREADDs in Drosophila: a pharmacogenetic approach for controlling behavior, neuronal signaling, and physiology in the fly.
abstract: 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.
authors.affiliation: Department of Pharmacology and Experimental Therapeutics, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA.
authors.forename: Jaime
authors.initials: J
authors.lastname: Becnel
authors.forename: Oralee
authors.initials: O
authors.lastname: Johnson
authors.forename: Zana R
authors.initials: ZR
authors.lastname: Majeed
authors.forename: Vi
authors.initials: V
authors.lastname: Tran
authors.forename: Bangning
authors.initials: B
authors.lastname: Yu
authors.forename: Bryan L
authors.initials: BL
authors.lastname: Roth
authors.forename: Robin L
authors.initials: RL
authors.lastname: Cooper
authors.forename: Edmund K
authors.initials: EK
authors.lastname: Kerut
authors.forename: Charles D
authors.initials: CD
authors.lastname: Nichols
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects* / Q000502:physiology; D015374:Biosensing Techniques; D015198:Designer Drugs / Q000737:chemistry / Q000494:pharmacology*; D004330:Drosophila / Q000187:drug effects* / Q000502:physiology*; D015195:Drug Design; D005260:Female; D008297:Male; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D015398:Signal Transduction
chemical_list: D015198:Designer Drugs