Drosophila Bitter Taste(s).

Most animals possess taste receptors neurons detecting potentially noxious compounds. In humans, the ligands which activate these neurons define a sensory space called "bitter". By extension, this term has been used in animals and insects to define molecules which induce aversive responses. In this review, based on our observations carried out in Drosophila, we examine how bitter compounds are detected and if bitter-sensitive neurons respond only to molecules bitter to humans. Like most animals, flies detect bitter chemicals through a specific population of taste neurons, distinct from those responding to sugars or to other modalities. Activating bitter-sensitive taste neurons induces aversive reactions and inhibits feeding. Bitter molecules also contribute to the suppression of sugar-neuron responses and can lead to a complete inhibition of the responses to sugar at the periphery. Since some bitter molecules activate bitter-sensitive neurons and some inhibit sugar detection, bitter molecules are represented by two sensory spaces which are only partially congruent. In addition to molecules which impact feeding, we recently discovered that the activation of bitter-sensitive neurons also induces grooming. Bitter-sensitive neurons of the wings and of the legs can sense chemicals from the gram negative bacteria, Escherichia coli, thus adding another biological function to these receptors. Bitter-sensitive neurons of the proboscis also respond to the inhibitory pheromone, 7-tricosene. Activating these neurons by bitter molecules in the context of sexual encounter inhibits courting and sexual reproduction, while activating these neurons with 7-tricosene in a feeding context will inhibit feeding. The picture that emerges from these observations is that the taste system is composed of detectors which monitor different "categories" of ligands, which facilitate or inhibit behaviors depending on the context (feeding, sexual reproduction, hygienic behavior), thus considerably extending the initial definition of "bitter" tasting.

Dual mechanism for bitter avoidance in Drosophila.

In flies and humans, bitter chemicals are known to inhibit sugar detection, but the adaptive role of this inhibition is often overlooked. At best, this inhibition is described as contributing to the rejection of potentially toxic food, but no studies have addressed the relative importance of the direct pathway that involves activating bitter-sensitive cells versus the indirect pathway represented by the inhibition of sugar detection. Using toxins to selectively ablate or inactivate populations of bitter-sensitive cells, we assessed the behavioral responses of flies to sucrose mixed with strychnine (which activates bitter-sensitive cells and inhibits sugar detection) or with L-canavanine (which only activates bitter-sensitive cells). As expected, flies with ablated bitter-sensitive cells failed to detect L-canavanine mixed with sucrose in three different feeding assays (proboscis extension responses, capillary feeding, and two-choice assays). However, such flies were still able to avoid strychnine mixed with sucrose. By means of electrophysiological recordings, we established that bitter molecules differ in their potency to inhibit sucrose detection and that sugar-sensing inhibition affects taste cells on the proboscis and the legs. The optogenetic response of sugar-sensitive cells was not reduced by strychnine, thus suggesting that this inhibition is linked directly to sugar transduction. We postulate that sugar-sensing inhibition represents a mechanism in insects to prevent ingesting harmful substances occurring within mixtures.

Consumption of bitter alkaloids in Drosophila melanogaster in multiple-choice test conditions.

Drosophila melanogaster adapt their food consumption to their internal needs and avoid ingesting noxious molecules. Defects in the genes involved in these decisions induce behavioral alterations that are usually screened by monitoring flies feeding in 2-choice or in no-choice situations. Here, we introduce a new behavioral test in which groups of flies are given access to 6 capillary feeders (MultiCAFE) containing fructose mixed with a serial dilution of a test substance. Using quinine, we first showed that fly density, distance between capillaries, and order of presentation have a minor impact on the discrimination performances of the flies. Fly discrimination was also only marginally affected by the type of test (no-choice, binary, or multiple-choice). Interestingly, the feeding reduction was well correlated with a reduction of the firing elicited by the mixture in sugar-sensitive gustatory receptor neurons, suggesting that several mechanisms concur to allow flies to make their choices. In addition to quinine, flies exhibited marked dose-dependent aversions to the consumption of berberine, caffeine, lobeline, nicotine, papaverine, strychnine, and theophylline, which all taste bitter to humans. Thus, despite of the multiplicity of choices available, flies consistently avoid alkaloids mixed with a sugar solution, and their choices are strongly dependent on their taste system. The MultiCAFE assay represents an interesting alternative to other feeding tests, in that it allows monitoring of the absolute consumption while also requiring less flies and time to run than other assays.