Amino acid taste is expected to be a universal property among animals. Although sweet, bitter, salt, and water tastes have been well characterized in insects, the mechanisms underlying amino acid taste remain elusive. From a Drosophila RNAi screen, we identify an ionotropic receptor, Ir76b, as necessary for yeast preference. Using calcium imaging, we identify Ir76b+ amino acid taste neurons in legs, overlapping partially with sweet neurons but not those that sense other tastants. Ir76b mutants have reduced responses to amino acids, which are rescued by transgenic expression of Ir76b and a mosquito ortholog AgIr76b. Co-expression of Ir20a with Ir76b is sufficient for conferring amino acid responses in sweet-taste neurons. Notably, Ir20a also serves to block salt response of Ir76b. Our study establishes the role of a highly conserved receptor in amino acid taste and suggests a mechanism for mutually exclusive roles of Ir76b in salt- and amino-acid-sensing neurons.

Mosquito-borne diseases affect hundreds of millions of people annually and disproportionately impact the developing world ^1,2 . One mosquito species, Aedes aegypti , is a primary vector of viruses that cause dengue, yellow fever and Zika. The attraction of Ae. aegypti female mosquitos to humans requires integrating multiple cues, including CO ₂ from breath, organic odours from skin and visual cues, all sensed at mid and long ranges, and other cues sensed at very close range ^3–6 . Here we identify a cue that Ae. aegypti use as part of their sensory arsenal to find humans. We demonstrate that Ae. aegypti sense the infrared (IR) radiation emanating from their targets and use this information in combination with other cues for highly effective mid-range navigation. Detection of thermal IR requires the heat-activated channel TRPA1, which is expressed in neurons at the tip of the antenna. Two opsins are co-expressed with TRPA1 in these neurons and promote the detection of lower IR intensities. We propose that radiant energy causes local heating at the end of the antenna, thereby activating temperature-sensitive receptors in thermosensory neurons. The realization that thermal IR radiation is an outstanding mid-range directional cue expands our understanding as to how mosquitoes are exquisitely effective in locating hosts.

Male courtship is provoked by perception of a potential mate. In addition, the likelihood and intensity of courtship are influenced by recent mating experience, which affects sexual drive. Using Drosophila melanogaster, we found that the homolog of mammalian neuropeptide Y, neuropeptide F (NPF), and a cluster of male-specific NPF (NPF^M) neurons, regulate courtship through affecting courtship drive. Disrupting NPF signaling produces sexually hyperactive males, which are resistant to sexual satiation, and whose courtship is triggered by sub-optimal stimuli. We found that NPF^M neurons make synaptic connections with P1 neurons, which comprise the courtship decision center. Activation of P1 neurons elevates NPF^M neuronal activity, which then act through NPF receptor neurons to suppress male courtship, and maintain the proper level of male courtship drive.

Significance: The taste of acids is critical for animal survival since it enables them to differentiate potentially dangerous from nutritious foods. Due to the general requirement for acid taste for survival, we tested the idea that the receptor mechanism functioning in acid taste may be evolutionarily conserved. Here, we demonstrate that mutation of a Drosophila gene, Otopetrin-Like A ( OtopLA ), encoding a protein distantly related to the recently identified mammalian acid taste receptor, OTOP1, is essential for both the strong repulsion to highly acidic food and mild attraction to low acidity. The mild attraction and strong aversion to acids requires expression of OtopLA in distinct taste neurons in the fly equivalent of the vertebrate tongue.

Food choice, in animals, has been known to change with internal nutritional state and also with variable dietary conditions. To better characterize mechanisms of diet-induced plasticity of food preference inDrosophila melanogaster, we synthesized diets with macronutrient imbalances and examined how food choice and taste sensitivity were modified in flies that fed on these diets. We found that dietary macronutrient imbalances caused compensatory behavioral shifts in both sexes to increase preference for the macronutrient that was scant in the food source, and simultaneously reduce preference for the macronutrient that was enriched. Further analysis with females revealed analogous changes in sweet taste responses in labellar neurons, with increased sensitivity on sugar-reduced diet and decreased sensitivity on sugar-enriched diet. Interestingly, we found differences in the onset of changes in taste sensitivity and behavior, which occur over 1–4 d, in response to dietary sugar reduction or enrichment. To investigate molecular mechanisms responsible for diet-induced taste modulation, we used candidate gene and transcriptome analyses. Our results indicate that signaling viaDop2Ris involved in increasing cellular and behavioral sensitivity to sugar as well as in decreasing behavioral sensitivity to amino acids on dietary sugar reduction. On the other hand, cellular and behavioral sensitivity to sugar relies ondilp5and a decrease in sugar preference following dietary sugar abundance was correlated with downregulation ofdilp5. Together, our results suggest that feeding preference for sugar and amino acid can be modulated independently to facilitate food choice that accounts for prior dietary experience.SIGNIFICANCE STATEMENTAnimals adjust their feeding preferences based on prior dietary experiences. Here, we find that upon dietary macronutrient deprivation, flies undergo compensatory changes in food preference. The altered preference correlates with changes in peripheral taste sensitivity. WhileDop2Rmediates changes following dietary sugar reduction, downregulation ofdilp5is associated with changes caused by a sugar-enriched diet. This study contributes to a better understanding of neurophysiological plasticity of the taste system in flies, and its role in facilitating adjustment of foraging behavior based on nutritional requirements.

High concentrations of dietary salt are harmful to health. Like most animals, Drosophila melanogaster are attracted to foods that have low concentrations of salt, but show strong taste avoidance of high salt foods. Salt in known on multiple classes of taste neurons, activating Gr64f sweet-sensing neurons that drive food acceptance and 2 others (Gr66a bitter and Ppk23 high salt) that drive food rejection. Here we find that NaCl elicits a bimodal dose-dependent response in Gr64f taste neurons, which show high activity with low salt and depressed activity with high salt. High salt also inhibits the sugar response of Gr64f neurons, and this action is independent of the neuron’s taste response to salt. Consistent with the electrophysiological analysis, feeding suppression in the presence of salt correlates with inhibition of Gr64f neuron activity, and remains if high salt taste neurons are genetically silenced. Other salts such as Na₂SO₄, KCl, MgSO₄, CaCl₂, and FeCl₃ act on sugar response and feeding behavior in the same way. A comparison of the effects of various salts suggests that inhibition is dictated by the cationic moiety rather than the anionic component of the salt. Notably, high salt-dependent inhibition is not observed in Gr66a neurons—response to a canonical bitter tastant, denatonium, is not altered by high salt. Overall, this study characterizes a mechanism in appetitive Gr64f neurons that can deter ingestion of potentially harmful salts.