Summary Animals are often confronted with the decision as to consume a diet that contains competing attractive and aversive compounds. Here, using the fruit fly, Drosophila melanogaster, we describe a mechanism that influences this decision. Addition of bitter compounds to sucrose suppressed feeding behavior, and this inhibition depended on the odorant binding protein, OBP49a. In wild-type flies, bitter compounds suppressed sucrose-induced action potentials, and the inhibition was impaired in Obp49a mutants. However, loss of OBP49a did not affect action potentials in sugar- or bitter-activated gustatory receptor neurons (GRNs) when the GRNs were presented with just one type of tastant. OBP49a was expressed in accessory cells, and acted non-cell autonomously to attenuate nerve firings in sugar-activated GRNs when bitter compounds were combined with sucrose. These findings demonstrate an unexpected role for an OBP in taste, and identify a molecular player involved in the integration of opposing attractive and aversive gustatory inputs.

Although several neural pathways have been implicated in feeding behaviors in mammals [1-7], it remains unclear how the brain coordinates feeding motivations to maintain a constant body weight (BW). Here, we identified a neuropeptide pathway important for the satiety and BW control in Drosophila. Silencing of myoinhibitory peptide (MIP) neurons significantly increased BW through augmented food intake and fat storage. Likewise, the loss-of-function mutation of mip also increased feeding and BW. Suppressing the MIP pathway induced satiated flies to behave like starved ones, with elevated sensitivity toward food. Conversely, activating MIP neurons greatly decreased food intake and BW and markedly blunted the sensitivity of starved flies toward food. Upon terminating the activation protocol of MIP neurons, the decreased BW reverts rapidly to the normal level through a strong feeding rebound, indicating the switch-like role of MIP pathway in feeding. Surprisingly, the MIP-mediated BW decrease occurred independently of sex peptide receptor (SPR), the only known receptor for MIP, suggesting the presence of a yet-unknown MIP receptor. Together, our results reveal a novel anorexigenic pathway that controls satiety in Drosophila and provide a new avenue to study how the brain actively maintains a constant BW.

Animals discriminate nutritious food from toxic substances using their sense of taste. Since taste perception requires taste receptor cells to come into contact with water-soluble chemicals, it is a form of contact chemosensation. Concurrent with that contact, mechanosensitive cells detect the texture of food and also contribute to the regulation of feeding. Little is known, however, about the extent to which chemosensitive and mechanosensitive circuits interact. Here, we show Drosophila prefers soft food at the expense of sweetness and that this preference requires labellar mechanosensory neurons (MNs) and the mechanosensory channel Nanchung. Activation of these labellar MNs causes GABAergic inhibition of sweet-sensing gustatory receptor neurons, reducing the perceived intensity of a sweet stimulus. These findings expand our understanding of the ways different sensory modalities cooperate to shape animal behaviour.

The ability to detect toxic compounds in foods is essential for animal survival. However, the minimal subunit composition of gustatory receptors required for sensing aversive chemicals in Drosophila is unknown. Here we report that three gustatory receptors, GR8a, GR66a and GR98b function together in the detection of L-canavanine, a plant-derived insecticide. Ectopic co-expression of Gr8a and Gr98b in Gr66a-expressing, bitter-sensing gustatory receptor neurons (GRNs) confers responsiveness to L-canavanine. Furthermore, misexpression of all three Grs enables salt- or sweet-sensing GRNs to respond to L-canavanine. Introduction of these Grs in sweet-sensing GRNs switches L-canavanine from an aversive to an attractive compound. Co-expression of GR8a, GR66a and GR98b in Drosophila S2 cells induces an L-canavanine-activated nonselective cation conductance. We conclude that three GRs collaborate to produce a functional L-canavanine receptor. Thus, our results clarify the full set of GRs underlying the detection of a toxic tastant that drives avoidance behaviour in an insect.

Animals must detect aversive compounds to survive. Bitter taste neurons express heterogeneous combinations of bitter receptors that diversify their response profiles, but this remains poorly understood. Here we describe groups of taste neurons in Drosophila that detect the same bitter compounds using unique combinations of gustatory receptors (GRs). These distinct complexes also confer responsiveness to non-overlapping sets of additional compounds. While either GR32a/GR59c/GR66a or GR22e/GR32a/GR66a heteromultimers are sufficient for lobeline, berberine, and denatonium detection, only GR22e/GR32a/GR66a responds to strychnine. Thus, despite minimal sequence-similarity, Gr22e and Gr59c show considerable but incomplete functional overlap. Since the gain- or loss-of-function of Gr22e or Gr59c alters bitter taste response profiles, we conclude a taste neuron’s specific combination of Grs determines its response profile. We suspect the heterogeneity of Gr expression in Drosophila taste neurons diversifies bitter compound detection, improving animal fitness under changing environmental conditions that present a variety of aversive compounds.

Objectives. Prognosticating idiopathic sudden sensorineural hearing loss (ISSNHL) is an important challenge. In our study, a dataset was split into training and test sets and cross-validation was implemented on the training set, thereby determining the hyperparameters for machine learning models with high test accuracy and low bias. The effectiveness of the following five machine learning models for predicting the hearing prognosis in patients with ISSNHL after 1 month of treatment was assessed: adaptive boosting, K-nearest neighbor, multilayer perceptron, random forest (RF), and support vector machine (SVM).Methods. The medical records of 523 patients with ISSNHL admitted to Korea University Ansan Hospital between January 2010 and October 2017 were retrospectively reviewed. In this study, we analyzed data from 227 patients (recovery, 106; no recovery, 121) after excluding those with missing data. To determine risk factors, statistical hypothesis tests (e.g., the two-sample t-test for continuous variables and the chi-square test for categorical variables) were conducted to compare patients who did or did not recover. Variables were selected using an RF model depending on two criteria (mean decreases in the Gini index and accuracy).Results. The SVM model using selected predictors achieved both the highest accuracy (75.36%) and the highest F-score (0.74) on the test set. The RF model with selected variables demonstrated the second-highest accuracy (73.91%) and F-score (0.74). The RF model with the original variables showed the same accuracy (73.91%) as that of the RF model with selected variables, but a lower F-score (0.73). All the tested models, except RF, demonstrated better performance after variable selection based on RF.Conclusion. The SVM model with selected predictors was the best-performing of the tested prediction models. The RF model with selected predictors was the second-best model. Therefore, machine learning models can be used to predict hearing recovery in patients with ISSNHL.

Regulation of feeding is essential for animal survival. The pharyngeal sense organs can act as a second checkpoint of food quality, due to their position between external taste organs such as the labellum which initially assess food quality, and the digestive tract. Growing evidence provides support that the pharyngeal sensory neurons regulate feeding, but much is still unknown. We found that a pair of gustatory receptor neurons in the LSO, a Drosophila adult pharyngeal organ which expresses four gustatory receptors, is involved in feeding inhibition in response to high concentrations of sodium ions. RNAi experiments and mutant analysis showed that the gustatory receptor Gr2a is necessary for this process. This feeding preference determined by whether a food source is perceived as appetizing or not is influenced by nutritional conditions, such that when the animal is hungry, the need for energy dominates over how appealing the food source is. Our results provide experimental evidence that factors involved in feeding function in a context-dependent manner.

The Journal of International Advanced Otology (J Int Adv Otol) is an international, peer reviewed, open access publication that is fully sponsored and owned by the European Academy of Otology and Neurotology and the Politzer Society. The journal is published triannually in April, August, and December and its publication language is English.The scope of the Journal is limited with otology, neurotology, audiology (excluding linguistics) and skull base medicine.The Journal of International Advanced Otology aims to publish manuscripts at the highest clinical and scientific level. J Int Adv Otol publishes original articles in the form of clinical and basic research, review articles, short reports and a limited number of case reports. Controversial patient discussions, communications on emerging technology, and historical issues will also be considered for publication.Target audience of J Int Adv Otol includes physicians and academics who work in the fields of otology, neurotology, audiology and skull base medicine.