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

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

doi:10.1016/j.celrep.2013.08.003

Cited by 42 publications

(31 citation statements)

References 48 publications

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“…To date, hM4Di (for silencing) and hM3Dq (for activating) neurons have been the most frequent used DREADDs. DREADDs have been used to modulate neural activity and behavior in flies (Becnel et al, 2013), mice (Alexander et al, 2009), rats (Ferguson et al, 2011), and nonhuman primates (Eldridge et al, 2016). Although DREADD technology has clearly been useful, there are several ways in which the technological platform could be enhanced.…”

Section: Areas For Enhancement Of Dreadd Technologiesmentioning

confidence: 99%

DREADDs for Neuroscientists

Roth

2016

Neuron

1,296

1,169

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To understand brain function, it is essential that we discover how cellular signaling specifies normal and pathological brain function. In this regard, chemogenetic technologies represent valuable platforms for manipulating neuronal and non-neuronal signal transduction in a cell-type-specific fashion in freely moving animals. Designer Receptors Exclusively Activated by Designer Drugs (DREADD)-based chemogenetic tools are now commonly used by neuroscientists to identify the circuitry and cellular signals that specify behavior, perceptions, emotions, innate drives, and motor functions in species ranging from flies to nonhuman primates. Here I provide a primer on DREADDs highlighting key technical and conceptual considerations and identify challenges for chemogenetics going forward.

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Section: Areas For Enhancement Of Dreadd Technologiesmentioning

confidence: 99%

DREADDs for Neuroscientists

Roth

2016

Neuron

1,296

1,169

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“…DREADD knock-in animal models, including Drosophila and mice, are currently being used by the GPCR research community for engaging celltype selective G protein signaling. For example, the selective expression of DREADDs in the Drosophila heart clarified the signal pathway of the 5-HT receptor in the control of heartbeat (Becnel et al, 2013;Majeed et al, 2013). DREADD/cloxipinenitric oxide pharmacology does not provide spatial-temporal control; however, there is no need for complex fiber/light-emitting diode systems or expensive microscopy, and this approach has therefore gained a wide user base.…”

Section: Model Organisms In Gpcr Researchmentioning

confidence: 99%

Model Organisms in G Protein–Coupled Receptor Research

et al. 2015

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The study of G protein-coupled receptors (GPCRs) has benefited greatly from experimental approaches that interrogate their functions in controlled, artificial environments. Working in vitro, GPCR receptorologists discovered the basic biologic mechanisms by which GPCRs operate, including their eponymous capacity to couple to G proteins; their molecular makeup, including the famed serpentine transmembrane unit; and ultimately, their three-dimensional structure. Although the insights gained from working outside the native environments of GPCRs have allowed for the collection of low-noise data, such approaches cannot directly address a receptor's native (in vivo) functions. An in vivo approach can complement the rigor of in vitro approaches: as studied in model organisms, it imposes physiologic constraints on receptor action and thus allows investigators to deduce the most salient features of receptor function. Here, we briefly discuss specific examples in which model organisms have successfully contributed to the elucidation of signals controlled through GPCRs and other surface receptor systems. We list recent examples that have served either in the initial discovery of GPCR signaling concepts or in their fuller definition. Furthermore, we selectively highlight experimental advantages, shortcomings, and tools of each model organism.

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“…We then confirm that SP is largely responsible for inducing this decrease, and demonstrate that the canonical sex peptide receptor (SPR) is necessary and acts in specific neurons to alter postmating sleep. Using a pharmacogenetic approach (Becnel et al, 2013), we establish that silencing the "canonical" SPSN-SAG postmating circuit is sufficient to decrease female sleep. Finally, experiments ablating the SPSN neurons suggest mechanistic differences in some PMRs.…”

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confidence: 99%

Changes in Female Drosophila Sleep following Mating Are Mediated by SPSN-SAG Neurons

et al. 2016

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Female Drosophila melanogaster, like many other organisms, exhibit different behavioral repertoires after mating with a male. These postmating responses (PMRs) include increased egg production and laying, increased rejection behavior (avoiding further male advances), decreased longevity, altered gustation and decreased sleep. Sex Peptide (SP), a protein transferred from the male during copulation, is largely responsible for many of these behavioral responses, and acts through a specific circuit to induce rejection behavior and alter dietary preference. However, less is known about the mechanisms and neurons that influence sleep in mated females. In this study, we investigated postmating changes in female sleep across strains and ages and on different media, and report that these changes are robust and relatively consistent under a variety of conditions. We find that female sleep is reduced by male-derived SP acting through the canonical sex peptide receptor (SPR) within the same neurons responsible for altering other PMRs. This circuit includes the SPSN-SAG neurons, whose silencing by DREADD induces postmating behaviors including sleep. Our data are consistent with the idea that mating status is communicated to the central brain through a common circuit that diverges in higher brain centers to modify a collection of postmating sensorimotor processes.

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

Cited by 42 publications

References 48 publications

DREADDs for Neuroscientists

DREADDs for Neuroscientists

Model Organisms in G Protein–Coupled Receptor Research

Changes in Female Drosophila Sleep following Mating Are Mediated by SPSN-SAG Neurons

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