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DREADDs in Drosophila: A Pharmacogenetic Approach for Controlling Behavior, Neuronal Signaling, and Physiology in the Fly

2013; Cell Press; Volume: 4; Issue: 5 Linguagem: Inglês

10.1016/j.celrep.2013.08.003

2639-1856

Jaime Becnel, Oralee Johnson, Zana R. Majeed, Vi Tran, Bangning Yu, Bryan L. Roth, Robin L. Cooper, Edmund Kenneth Kerut, Charles D. Nichols,

Photoreceptor and optogenetics research

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.