Jing W. Wang

All metazoan guts harbor commensal communities, from a dozen bacterial species in Drosophila to hundreds in humans. Here, we condition flies with diets containing varying levels of protein and sugar to investigate the impact of dietary history on the interaction between commensal gut bacteria and feeding adaptation in Drosophila. We find that appetite increases with dietary protein, dependent on total gut bacteria content, and enhanced by a drug that promotes the growth of short-chain fatty acid (SCFA)-producing gut bacteria. Lactiplantibacillus is a potential source of butyrate, while Acetobacter produces acetate. Mono-association with Acetobacter or Lactiplantibacillus increases food intake. Mutant strains unable to produce acetate or butyrate have lesser effects. Finally, adding acetate or butyrate to conditioning diets recapitulates the appetitive effect of Acetobacter and Lactiplantibacillus, respectively. Our findings suggest that protein-enriched diets enhance appetite by promoting the interaction between commensal bacteria and the host, with bacterial SCFAs as a conduit.

Animals must set behavioural priority in a context-dependent manner and switch from one behaviour to another at the appropriate moment^1,2,3. Here we probe the molecular and neuronal mechanisms that orchestrate the transition from feeding to courtship in Drosophila melanogaster. We find that feeding is prioritized over courtship in starved males, and the consumption of protein-rich food rapidly reverses this order within a few minutes. At the molecular level, a gut-derived, nutrient-specific neuropeptide hormone—Diuretic hormone 31 (Dh31)—propels a switch from feeding to courtship. We further address the underlying kinetics with calcium imaging experiments. Amino acids from food acutely activate Dh31⁺ enteroendocrine cells in the gut, increasing Dh31 levels in the circulation. In addition, three-photon functional imaging of intact flies shows that optogenetic stimulation of Dh31⁺ enteroendocrine cells rapidly excites a subset of brain neurons that express Dh31 receptor (Dh31R). Gut-derived Dh31 excites the brain neurons through the circulatory system within a few minutes, in line with the speed of the feeding–courtship behavioural switch. At the circuit level, there are two distinct populations of Dh31R⁺ neurons in the brain, with one population inhibiting feeding through allatostatin-C and the other promoting courtship through corazonin. Together, our findings illustrate a mechanism by which the consumption of protein-rich food triggers the release of a gut hormone, which in turn prioritizes courtship over feeding through two parallel pathways.

Hemolymph is driven through the antennae of Drosophila melanogaster by the rhythmic contraction of muscle 16 (m16), which runs through the brain. Contraction of m16 results in the expansion of an elastic ampulla, opening ostia and filling the ampulla. Relaxation of the ampullary membrane forces hemolymph through vessels into the antennae. We show that m16 is an auto-active rhythmic somatic muscle. The activity of m16 leads to the rapid perfusion of the antenna by hemolymph. In addition, it leads to the rhythmic agitation of the brain, which could be important for clearing the interstitial space.

Several techniques have been developed to manipulate gene expression temporally in intact neural circuits. However, the applicability of current tools developed for in vivo studies in Drosophila is limited by their incompatibility with existing GAL4 lines and side effects on physiology and behavior. To circumvent these limitations, we adopted a strategy to reversibly regulate protein degradation with a small molecule by using a destabilizing domain (DD). We show that this system is effective across different tissues and developmental stages. We further show that this system can be used to control in vivo gene expression levels with low background, large dynamic range, and in a reversible manner without detectable side effects on the lifespan or behavior of the animal. Additionally, we engineered tools for chemically controlling gene expression (GAL80-DD) and recombination (FLP-DD). We demonstrate the applicability of this technology in manipulating neuronal activity and for high-efficiency sparse labeling of neuronal populations.

The overall goal of this protocol is to demonstrate how to present odorants of low volatility for single-sensillum recording from...

Animals are born with a rich repertoire of robust behaviors that are critical for their survival. However, innate behaviors are also highly adaptable to an animal's internal state and external environment. Neuromodulators, including biogenic amines, neuropeptides, and hormones, are released to signal changes in animals’ circumstances and serve to reconfigure neural circuits. This circuit flexibility allows animals to modify their behavioral responses according to environmental cues, metabolic demands, and physiological states. Aided by powerful genetic tools, researchers have made remarkable progress in Drosophila melanogaster to address how a myriad of contextual information influences the input-output relationship of hardwired circuits that support a complex behavioral repertoire. Here we highlight recent advances in understanding neuromodulation of Drosophila innate behaviors, with a special focus on feeding, courtship, aggression, and postmating behaviors.

Several techniques have been developed to manipulate gene expression temporally in intact neural circuits. However, the applicability of current tools developed for in vivo studies in Drosophila is limited by their incompatibility with existing GAL4 lines and side effects on physiology and behavior. To circumvent these limitations, we adopted a strategy to reversibly regulate protein degradation with a small molecule by using a destabilizing domain (DD). We show that this system is effective across different tissues and developmental stages. We further show that this system can be used to control in vivo gene expression levels with low background, large dynamic range, and in a reversible manner without detectable side effects on the lifespan or behavior of the animal. Additionally, we engineered tools for chemically controlling gene expression (GAL80-DD) and recombination (FLP-DD). We demonstrate the applicability of this technology in manipulating neuronal activity and for high-efficiency sparse labeling of neuronal populations.