The Cellular and Molecular Basis of Sour Taste.

Sour taste, the taste of acids, is one of the most enigmatic of the five basic taste qualities; its function is unclear and its receptor was until recently unknown. Sour tastes are transduced in taste buds on the tongue and palate epithelium by a subset of taste receptor cells, known as type III cells. Type III cells express a number of unique markers, which allow for their identification and manipulation. These cells respond to acid stimuli with action potentials and release neurotransmitters onto afferent nerve fibers, with cell bodies in geniculate and petrosal ganglia. Here, we review classical studies of sour taste leading up to the identification of the sour receptor as the proton channel OTOP1.

Neuronal Activity in the Gustatory Cortex during Economic Choice.

An economic choice entails computing and comparing the values of individual offers. Offer values are represented in the orbitofrontal cortex (OFC)-an area that participates in value comparison-but it is unknown where offer values are computed in the first place. One possibility is that this computation takes place in OFC. Alternatively, offer values might be computed upstream of OFC. For choices between edible goods, a primary candidate is the gustatory region of the anterior insula (gustatory cortex, GC). Here we recorded from the GC of male rhesus monkeys choosing between different juice types. As a population, neurons in GC represented the flavor, the quantity, and the subjective value of the juice chosen by the animal. These variables were represented by distinct groups of cells and with different time courses. Specifically, chosen value signals emerged shortly after offer presentation, while neurons encoding the chosen juice and the chosen quantity peaked after juice delivery. Surprisingly, neurons in GC did not represent individual offer values in a systematic way. In a computational sense, the variables encoded in GC follow the process of value comparison. Thus our results argue against the hypothesis that offer values are computed in GC. At the same time, signals representing the subjective value of the expected reward indicate that responses in GC are not purely sensory. Thus neuronal responses in GC appear consummatory in nature.

Multisensory Integration Underlies the Distinct Representation of Odor-Taste Mixtures in the Gustatory Cortex of Behaving Rats.

The perception of food relies on the integration of olfactory and gustatory signals originating from the mouth. This multisensory process generates robust associations between odors and tastes, significantly influencing the perceptual judgment of flavors. However, the specific neural substrates underlying this integrative process remain unclear. Previous electrophysiological studies identified the gustatory cortex as a site of convergent olfactory and gustatory signals, but whether neurons represent multimodal odor-taste mixtures as distinct from their unimodal odor and taste components is unknown. To investigate this, we recorded single-unit activity in the gustatory cortex of behaving female rats during the intraoral delivery of individual odors, individual tastes, and odor-taste mixtures. Our results demonstrate that chemoselective neurons in the gustatory cortex are broadly responsive to intraoral chemosensory stimuli, exhibiting time-varying multiphasic changes in activity. In a subset of these chemoselective neurons, odor-taste mixtures elicit nonlinear cross-modal responses that distinguish them from their olfactory and gustatory components. These findings provide novel insights into multimodal chemosensory processing by the gustatory cortex, highlighting the distinct representation of unimodal and multimodal intraoral chemosensory signals. Overall, our findings suggest that olfactory and gustatory signals interact nonlinearly in the gustatory cortex to enhance the identity coding of both unimodal and multimodal chemosensory stimuli.

Internal sensory neurons regulate stage-specific growth in Drosophila.

Animals control their developmental schedule in accordance with internal states and external environments. In Drosophila larvae, it is well established that nutrient status is sensed by different internal organs, which in turn regulate production of insulin-like peptides and thereby control growth. In contrast, the impact of the chemosensory system on larval development remains largely unclear. Here, we performed a genetic screen to identify gustatory receptor (Gr) neurons regulating growth and development, and found that Gr28a-expressing neurons are required for proper progression of larval growth. Gr28a is expressed in a subset of peripheral internal sensory neurons, which directly extend their axons to insulin-producing cells (IPCs) in the central nervous system. Silencing of Gr28a-expressing neurons blocked insulin-like peptide release from IPCs and suppressed larval growth during the mid-larval period. These results indicate that Gr28a-expressing neurons promote larval development by directly regulating growth-promoting endocrine signaling in a stage-specific manner.

Inhibitory Gating of Thalamocortical Inputs onto Rat Gustatory Insular Cortex.

In primary gustatory cortex (GC), a subregion of the insular cortex, neurons show anticipatory activity, encode taste identity and palatability, and their activity is related to decision-making. Inactivation of the gustatory thalamus, the parvicellular region of the ventral posteromedial thalamic nucleus (VPMpc), dramatically reduces GC taste responses, consistent with the hypothesis that VPMpc-GC projections carry taste information. Recordings in awake rodents reported that taste-responsive neurons can be found across GC, without segregated spatial mapping, raising the possibility that projections from the taste thalamus may activate GC broadly. In addition, we have shown that cortical inhibition modulates the integration of thalamic and limbic inputs, revealing a potential role for GABA transmission in gating sensory information to GC. Despite this wealth of information at the system level, the synaptic organization of the VPMpc-GC circuit has not been investigated. Here, we used optogenetic activation of VPMpc afferents to GC in acute slice preparations from rats of both sexes to investigate the synaptic properties and organization of VPMpc afferents in GC and their modulation by cortical inhibition. We hypothesized that VPMpc-GC synapses are distributed across GC, but show laminar- and cell-specific properties, conferring computationally flexibility to how taste information is processed. We also found that VPMpc-GC synaptic responses are strongly modulated by the activity regimen of VPMpc afferents, as well as by cortical inhibition activating GABAA and GABAB receptors onto VPMpc terminals. These results provide a novel insight into the complex features of thalamocortical circuits for taste processing.SIGNIFICANCE STATEMENT We report that the input from the primary taste thalamus to the primary gustatory cortex (GC) shows distinct properties compared with primary thalamocortical synapses onto other sensory areas. Ventral posteromedial thalamic nucleus afferents in GC make synapses with excitatory neurons distributed across all cortical layers and display frequency-dependent short-term plasticity to repetitive stimulation; thus, they do not fit the classic distinction between drivers and modulators typical of other sensory thalamocortical circuits. Thalamocortical activation of GC is gated by cortical inhibition, providing local corticothalamic feedback via presynaptic ionotropic and metabotropic GABA receptors. The connectivity and inhibitory control of thalamocortical synapses in GC highlight unique features of the thalamocortical circuit for taste.

Coupled Dynamics of Stimulus-Evoked Gustatory Cortical and Basolateral Amygdalar Activity.

Gustatory cortical (GC) single-neuron taste responses reflect taste quality and palatability in successive epochs. Ensemble analyses reveal epoch-to-epoch firing-rate changes in these responses to be sudden, coherent transitions. Such nonlinear dynamics suggest that GC is part of a recurrent network, producing these dynamics in concert with other structures. Basolateral amygdala (BLA), which is reciprocally connected to GC and central to hedonic processing, is a strong candidate partner for GC, in that BLA taste responses evolve on the same general clock as GC and because inhibition of activity in the BLA→GC pathway degrades the sharpness of GC transitions. These facts motivate, but do not test, our overarching hypothesis that BLA and GC act as a single, comodulated network during taste processing. Here, we provide just this test of simultaneous (BLA and GC) extracellular taste responses in female rats, probing the multiregional dynamics of activity to directly test whether BLA and GC responses contain coupled dynamics. We show that BLA and GC response magnitudes covary across trials and within single responses, and that changes in BLA-GC local field potential phase coherence are epoch specific. Such classic coherence analyses, however, obscure the most salient facet of BLA-GC coupling: sudden transitions in and out of the epoch known to be involved in driving gaping behavior happen near simultaneously in the two regions, despite huge trial-to-trial variability in transition latencies. This novel form of inter-regional coupling, which we show is easily replicated in model networks, suggests collective processing in a distributed neural network.SIGNIFICANCE STATEMENT There has been little investigation into real-time communication between brain regions during taste processing, a fact reflecting the dominant belief that taste circuitry is largely feedforward. Here, we perform an in-depth analysis of real-time interactions between GC and BLA in response to passive taste deliveries, using both conventional coherence metrics and a novel methodology that explicitly considers trial-to-trial variability and fast single-trial dynamics in evoked responses. Our results demonstrate that BLA-GC coherence changes as the taste response unfolds, and that BLA and GC specifically couple for the sudden transition into (and out of) the behaviorally relevant neural response epoch, suggesting (although not proving) that: (1) recurrent interactions subserve the function of the dyad as (2) a putative attractor network.

The Human Centromedial Amygdala Contributes to Negative Prediction Error Signaling during Appetitive and Aversive Pavlovian Gustatory Learning.

Prediction error (PE) is the mismatch between a prior expectation and reality, and it lies at the core of associative learning about aversive and appetitive stimuli. Human studies on fear learning have linked the amygdala to aversive PEs. In contrast, the relationship between the amygdala and PE in appetitive settings and stimuli, unlike those that induce fear, has received less research attention. Animal studies show that the amygdala is a functionally heterogeneous structure. Nevertheless, the role of the amygdala nuclei in PE signaling remains unknown in humans. To clarify the role of two subdivisions of the human amygdala, the centromedial amygdala (CMA) and basolateral amygdala (BLA), in appetitive and aversive PE signaling, we used gustatory pavlovian learning involving eating-related naturalistic outcomes. Thirty-eight right-handed individuals (19 females) participated in the study. We found that surprise with neutral feedback when a reward is expected triggers activity within the left and right CMA. When an aversive outcome is expected, surprise with neutral feedback triggers activity only within the left CMA. Notably, the BLA was not activated by those conditions. Thus, the CMA engages in negative PE signaling during appetitive and aversive gustatory pavlovian learning, whereas the BLA is not critical for this process. In addition, PE-related activity within the left CMA during aversive learning is negatively correlated with neuroticism and positively correlated with extraversion. The findings indicate the importance of the CMA in gustatory learning when the value of outcomes changes and have implications for understanding psychological conditions that manifest perturbed processing of negative PEs.SIGNIFICANCE STATEMENT A discrepancy between a prediction and an actual outcome (PE) plays a crucial role in learning. Learning improves when an outcome is more significant than expected (positive PE) and worsens when it is smaller than expected (negative PE). We found that the negative PE during appetitive and aversive taste learning is associated with increased activity of the CMA, which suggests that the CMA controls taste learning. Our findings may have implications for understanding psychological states associated with deficient learning from negative PEs, such as obesity and addictive behaviors.

De novo assembly and annotation of Popillia japonica's genome with initial clues to its potential as an invasive pest.

BACKGROUND: The spread of Popillia japonica in non-native areas (USA, Canada, the Azores islands, Italy and Switzerland) poses a significant threat to agriculture and horticulture, as well as to endemic floral biodiversity, entailing that appropriate control measures must be taken to reduce its density and limit its further spread. In this context, the availability of a high quality genomic sequence for the species is liable to foster basic research on the ecology and evolution of the species, as well as on possible biotechnologically-oriented and genetically-informed control measures. RESULTS: The genomic sequence presented and described here is an improvement with respect to the available draft sequence in terms of completeness and contiguity, and includes structural and functional annotations. A comparative analysis of gene families of interest, related to the species ecology and potential for polyphagy and adaptability, revealed a contraction of gustatory receptor genes and a paralogous expansion of some subgroups/subfamilies of odorant receptors, ionotropic receptors and cytochrome P450s. CONCLUSIONS: The new genomic sequence as well as the comparative analyses data may provide a clue to explain the staggering invasive potential of the species and may serve to identify targets for potential biotechnological applications aimed at its control.

Few chemoreceptor genes in the ambrosia beetle Trypodendron lineatum may reflect its specialized ecology.

BACKGROUND: Chemoreception is crucial for insect fitness, underlying for instance food-, host-, and mate finding. Chemicals in the environment are detected by receptors from three divergent gene families: odorant receptors (ORs), gustatory receptors (GRs), and ionotropic receptors (IRs). However, how the chemoreceptor gene families evolve in parallel with ecological specializations remains poorly understood, especially in the order Coleoptera. Hence, we sequenced the genome and annotated the chemoreceptor genes of the specialised ambrosia beetle Trypodendron lineatum (Coleoptera, Curculionidae, Scolytinae) and compared its chemoreceptor gene repertoires with those of other scolytines with different ecological adaptations, as well as a polyphagous cerambycid species. RESULTS: We identified 67 ORs, 38 GRs, and 44 IRs in T. lineatum ('Tlin'). Across gene families, T. lineatum has fewer chemoreceptors compared to related scolytines, the coffee berry borer Hypothenemus hampei and the mountain pine beetle Dendroctonus ponderosae, and clearly fewer receptors than the polyphagous cerambycid Anoplophora glabripennis. The comparatively low number of chemoreceptors is largely explained by the scarcity of large receptor lineage radiations, especially among the bitter taste GRs and the 'divergent' IRs, and the absence of alternatively spliced GR genes. Only one non-fructose sugar receptor was found, suggesting several sugar receptors have been lost. Also, we found no orthologue in the 'GR215 clade', which is widely conserved across Coleoptera. Two TlinORs are orthologous to ORs that are functionally conserved across curculionids, responding to 2-phenylethanol (2-PE) and green leaf volatiles (GLVs), respectively. CONCLUSIONS: Trypodendron lineatum reproduces inside the xylem of decaying conifers where it feeds on its obligate fungal mutualist Phialophoropsis ferruginea. Like previous studies, our results suggest that stenophagy correlates with small chemoreceptor numbers in wood-boring beetles; indeed, the few GRs may be due to its restricted fungal diet. The presence of TlinORs orthologous to those detecting 2-PE and GLVs in other species suggests these compounds are important for T. lineatum. Future functional studies should test this prediction, and chemoreceptor annotations should be conducted on additional ambrosia beetle species to investigate whether few chemoreceptors is a general trait in this specialized group of beetles.

Nanofluidic Membrane-Assisted Organic Electrochemical Transistors for Bioinspired Gustatory Sensation Based on Selective Cation Transport.

Natural organisms have evolved precise sensing systems relying on unique ion channels, which can efficiently perceive various physical/chemical stimuli based on ionic signal transmission in biological fluid environments. However, it is still a huge challenge to achieve extensive applications of the artificial counterparts as an efficient wet sensing platform due to the fluidity of the working medium. Herein, nanofluidic membranes with selective cation transport properties and solid-state organic electrochemical transistors (OECTs) with amplified signals are integrated together to mimic human gustatory sensation, achieving ionic gustatory reagent recognition and a portable configuration. Cu-HHTP nanofluidic membranes with selective cation transport through their uniform micropores are constructed first, followed by assembly with OECTs to form the designed nanofluidic membrane-assisted OECTs (nanofluidic OECTs). As a result, they can distinguish typically ionic gustatory reagents, and even ionic liquids (ILs), demonstrating enhanced gustatory perception performance under a wide concentration range (10-7-10-1 m) compared with those of conventional OECTs. The linear correlations between the response and the reagent concentration further indicate the promising potential for practical application as a next-generation sensing platform. It is suggested that nanofluidic membranes mediated intramembrane cation transport based on the steric hindrance effect, resulting in distinguishable and improved response to multiple ions.

Cyclophosphamide induces the loss of taste bud innervation in mice.

Many common chemotherapeutics produce disruptions in the sense of taste which can lead to loss of appetite, nutritional imbalance, and reduced quality of life, especially if taste loss persists after treatment ends. Cyclophosphamide (CYP), an alkylating chemotherapeutic agent, affects taste sensitivity through its cytotoxic effects on mature taste receptor cells (TRCs) and on taste progenitor cell populations, retarding the capacity to replace TRCs. Mechanistic studies have focused primarily on taste cells, however, taste signaling requires communication between TRCs and the gustatory nerve fibers that innervate them. Here, we evaluate cyclophosphamide's effects on the peripheral gustatory nerve fibers that innervate the taste buds. Following histological analysis of tongue tissues, we find that CYP reduces innervation within the fungiform and circumvallates taste buds within 4 days after administration. To better understand the dynamics of the denervation process, we used 2-photon intravital imaging to visualize the peripheral gustatory nerve fibers within individual fungiform taste buds up to 20 days after CYP treatment. We find that gustatory fibers retract from the taste bud properly but are maintained within the central papilla core. These data indicate that in addition to TRCs, gustatory nerve fibers are also affected by CYP treatment. Because the connectivity between TRCs and gustatory neurons must be re-established for proper function, gustatory fibers should continue to be included in future studies to understand the mechanisms leading to chemotherapy-induced persistent taste loss.

Chemosensory detection of glucosinolates as token stimuli for specialist insects on brassicaceous plants: discovery and impact.

In this paper, we take a historical perspective by going back to Verschaffelt's landmark study published in 1910, in which he found that glucosinolates were used as token stimuli by larvae of Pieris butterflies, specialist feeders on plants in the family Brassicaceae. This classic discovery provided key evidence for Fraenkel (Science 129:1466-1470, 1959) to elaborate on the function of secondary plant substances and for Ehrlich and Raven (Evolution 18:586-608, 1964) to put forward the hypothesis of insect-plant coevolution. The discovery by Schoonhoven (Kon Nederl Akad Wetensch Amsterdam Proc Ser C70:556-568, 1967) of taste neurons highly sensitive to glucosinolates in Pieris brassicae was an important milestone in elucidating the chemosensory basis of host-plant specialization. The molecular basis of glucosinolate sensitivity was elucidated recently (Yang et al., PLoS Genet 17, 2021) paving the way to unravel the evolution of gustatory receptors tuned to glucosinolates that are crucial for host-plant selection of Pieris butterflies. We propose a hypothetical model for the evolution of labeled-line neurons tuned to token stimuli.

Gustatory dysfunction and long COVID in Chinese patients with COVID-19: A 6-month follow-up study.

AIMS: To evaluate long COVID of gustatory dysfunction and the associated risk factors regarding onset and recovery in Chinese patients. METHODS: We conducted a cross-sectional study of patients with SARS-CoV-2 Omicron infection at Changxing Mobile Cabin Hospital in Shanghai, China, from March to May 2022. A prospective follow-up of patients with gustatory dysfunction was conducted at 6 months after discharge. RESULTS: In total, 18.48% (241/1304) reported gustatory dysfunction. The 6-month follow-up response rate was 89.63% (216/241) and 74.02% recovered their taste sense within 1-3 weeks. A total of 20.37% of patients (44/216) presented with long COVID. Symptoms persisted for 12 patients (5.56%) after 6 months. Having multiple taste impairments (OR, 2.364; 95% CI, 1.286-4.348; p = 0.006) was associated with a higher risk of gustatory dysfunction with long COVID. Having received a COVID-19 vaccine booster was positively associated with taste sensation recovery (HR, 1.344; 95% CI, 1.012-1.785; p = 0.041). CONCLUSIONS: About 20.37% of patients with COVID-19 might develop long COVID of gustatory dysfunction and 5.56% with persisting changes in their sense of taste. Most patients recovered taste sensations within 1-3 weeks after COVID-19 symptom onset and receiving a booster shot of the COVID-19 vaccine presented a protective effect on the taste sensation recovery.

Adherence to mediterranean diet and aromatic plants intake are related with gustatory function: A case-study from a Portuguese region.

The Mediterranean Diet has been recognized as one of the healthiest and most sustainable dietary patterns and is flavor rich due to the use of different seasonings, such as aromatic plants, in dish confection. Based on the hypotheses that: 1) gustatory function will affect food choices; 2) seasoning flavors may be differently accepted according to individuals' gustatory functions; the aim of the present study was to assess the association between taste sensitivity and/or preference with Mediterranean Diet adherence and seasoning consumption. A total of 383 adults (18-59 years old; 198 female, 185 male) from North Alentejo region of Portugal were enrolled in this study, with 291 (145 female and 146 male) also evaluated for gustatory function. Recognition thresholds were obtained for four tastes (sweet, sour, salty, and bitter) and astringency, as well as preference level for the highest concentration of each stimulus tested. A validated Food Frequency Questionnaire was filled out, and MD adherence was extrapolated from the answers of the Food Frequency Questionnaire according to the Mediterranean Diet Adherence Screener (MEDAS) score. In total, 20.8% of the individuals presented low, 58.2% medium, and 21.0% high adherence. Adherence was higher in women than men and in older individuals than younger adults. Adherence to the Mediterranean Diet was positively correlated with aromatic plants consumption but not spices. Seasonings were associated with gustatory function, and the cluster with higher consumption presented higher preferences for bitter and salty tastes. Total sodium intake was also higher in this cluster, suggesting that these individuals prefer stronger oral sensations. In conclusion, this study shows that MD adherence is not high, even in regions with rural characteristics. The observed association of MD and seasoning intake with gustatory function do underline the usefulness of this information in strategies aimed at promoting healthy and sustainable eating patterns.

Interoceptive abilities impairment correlates with emotional eating and taste abnormalities in children with overweight and obesity.

Weight problems in children are associated with emotional eating, which has been linked to interoceptive abilities. Previous research also shows altered olfactory and gustatory perception in children with obesity and overweight. Therefore, we aimed to investigate the connection of alterations in olfactory and gustatory perception to interoceptive abilities and emotional eating among children with obesity and overweight. 23 children with overweight and obesity and age-matched controls with normal weight (12-16 years old) underwent olfactory and gustatory testing. Interoceptive abilities were assessed, focusing on interoceptive accuracy and interoceptive sensibility. Children with overweight and obesity showed significantly higher accuracy for detection of sweet taste, but descriptively lower accuracy for all other taste qualities compared to normal weight children. We found no changes in olfactory abilities in children with overweight and obesity. Emotional eating scores were elevated for children with overweight and obesity, and interoceptive accuracy scores were significantly lower. In both groups, interoceptive accuracy was inversely correlated with emotional eating. Our results support prior findings of altered gustatory abilities in children with overweight and obesity. The observed link between impaired interoceptive processes and heightened emotional eating in this group implies that interventions for overweight in children could benefit from targeting interoceptive abilities. This study provides meaningful grounds for further investigations into the roles of taste, emotional eating, and interoceptive abilities for overweight in children and adolescents.

Home screening of taste and oral trigeminal function: a feasibility study.

PURPOSE: gustatory ability is a marker of health not routinely tested in the medical practice. The current study wants to assess whether taste strips can be useful to monitor taste function from home. METHODS: we performed simple sensory tests in lab setting vs. unassisted testing at home, and compared the results with self-reports ability to taste and smell. Using paper strips impregnated with sweet, bitter, salty, or sour tastants, and with two trigeminal stimuli (capsaicin, tannins) in high and low concentrations, we assessed gustatory and trigeminal function in 74 participants (47 women) in the lab, where paper strips were administered by an experimenter, and in 77 participants (59 women) at home, where they self-administered the test. RESULTS: we found that high (but not low) concentration taste strips are correctly identified by vast majority of participants. On average, taste identification, intensity and pleasantness scores did not differ for the 8 taste strips, while identification of capsaicin was significantly better in the lab. Taste identification scores correlated with intensity ratings in both settings (r = 0.56, in the lab, r = 0.48, at home, p < 0.005). Self-rated taste ability correlated with self-rated smell ability (r = 0.68, and r = 0.39, p ≤ 0.005), but not with scores in the strips test. CONCLUSION: home testing with impregnated taste strips is feasible, and can be used for telemedical purposes.

Molecular Basis of CO2 Sensing in Hyphantria cunea.

Carbon dioxide (CO2) released by plants can serve as a cue for regulating insect behaviors. Hyphantria cunea is a widely distributed forestry pest that may use CO2 as a cue for foraging and oviposition. However, the molecular mechanism underlying its ability to sense CO2 has not been elucidated. Our initial study showed that CO2 is significantly attractive to H. cunea adults. Subsequently, 44 H. cunea gustatory receptors (GRs) were identified using transcriptome data, and 3 candidate CO2 receptors that are specifically expressed in the labial palps were identified. In vivo electrophysiological assays revealed that the labial palp is the primary organ for CO2 perception in H. cunea, which is similar to findings in other lepidopteran species. By using the Xenopus oocyte expression system, we showed that the HcunGR1 and HcunGR3 co-expressions produced a robust response to CO2, but HcunGR2 had an inhibitory effect on CO2 perception. Finally, immunohistochemical staining revealed sexual dimorphism in the CO2-sensitive labial pit organ glomerulus (LPOG). Taken together, our results clarified the mechanism by which H. cunea sense CO2, laying the foundation for further investigations into the role of CO2 in the rapid spread of H. cunea.

Factors associated with impaired psychophysical gustatory function.

OBJECTIVE: To investigate the clinical characteristics associated with measured gustatory dysfunction in patients with chemosensory (smell and taste) discomfort. STUDY DESIGN: Retrospective study. DESIGN: Hospital-based cohort. SETTING: The clinical characteristics associated with the measured diagnosis of gustatory dysfunction were statistically analysed. PARTICIPANTS: Patients who underwent all the psychophysical olfactory and chemical gustatory function tests (YSK olfactory function test and chemical gustometry exam) and the subjective questionnaires between October 2021 and February 2023. MAIN OUTCOME MEASURES: YSK olfactory function test and chemical gustometry results, subjective questionnaire score about chemosensory (smell and taste) functions. The Medical records of patients who visited the smell and taste centre in a tertiary. RESULTS: A total of 219 patients were enrolled; 180 were diagnosed as having normal gustatory function, and 39 were diagnosed as having gustatory dysfunction. Subjective recognition of gustatory function was not associated with the measured gustatory function. Age, sex, measured olfactory function and the threshold and discrimination scores for the olfactory function test were significant factors in the multivariate analysis. When the patients were further divided according to age, the threshold test scores rather than other subsets in the olfactory function test were significantly associated with measured gustatory dysfunction in patients 60 and older. CONCLUSION: In older adult male patients with olfactory dysfunction, gustatory function should be considered regardless of subjective gustatory dysfunction.

Bacteria-Derived Peptidoglycan Triggers a Noncanonical Nuclear Factor-κB-Dependent Response in Drosophila Gustatory Neurons.

Probing the external world is essential for eukaryotes to distinguish beneficial from pathogenic micro-organisms. If it is clear that the main part of this task falls to the immune cells, recent work shows that neurons can also detect microbes, although the molecules and mechanisms involved are less characterized. In Drosophila, detection of bacteria-derived peptidoglycan by pattern recognition receptors of the peptidoglycan recognition protein (PGRP) family expressed in immune cells triggers nuclear factor-κB (NF-κB)/immune deficiency (IMD)-dependent signaling. We show here that one PGRP protein, called PGRP-LB, is expressed in bitter gustatory neurons of proboscises. In vivo calcium imaging in female flies reveals that the PGRP/IMD pathway is cell-autonomously required in these neurons to transduce the peptidoglycan signal. We finally show that NF-κB/IMD pathway activation in bitter-sensing gustatory neurons influences fly behavior. This demonstrates that a major immune response elicitor and signaling module are required in the peripheral nervous system to sense the presence of bacteria in the environment.SIGNIFICANCE STATEMENT In addition to the classical immune response, eukaryotes rely on neuronally controlled mechanisms to detect microbes and engage in adapted behaviors. However, the mechanisms of microbe detection by the nervous system are poorly understood. Using genetic analysis and calcium imaging, we demonstrate here that bacteria-derived peptidoglycan can activate bitter gustatory neurons. We further show that this response is mediated by the PGRP-LC membrane receptor and downstream components of a noncanonical NF-κB signaling cascade. Activation of this signaling cascade triggers behavior changes. These data demonstrate that bitter-sensing neurons and immune cells share a common detection and signaling module to either trigger the production of antibacterial effectors or to modulate the behavior of flies that are in contact with bacteria. Because peptidoglycan detection doesn't mobilize the known gustatory receptors, it also demonstrates that taste perception is much more complex than anticipated.

A Drosophila Circuit for Habituation Override.

Habituated animals retain a latent capacity for robust engagement with familiar stimuli. In most instances, the ability to override habituation is best explained by postulating that habituation arises from the potentiation of inhibitory inputs onto stimulus-encoding assemblies and that habituation override occurs through disinhibition. Previous work has shown that inhibitory plasticity contributes to specific forms of olfactory and gustatory habituation in Drosophila Here, we analyze how exposure to a novel stimulus causes override of gustatory (proboscis extension reflex; PER) habituation. While brief sucrose contact with tarsal hairs causes naive Drosophila to extend their proboscis, persistent exposure reduces PER to subsequent sucrose stimuli. We show that in so habituated animals, either brief exposure of the proboscis to yeast or direct thermogenetic activation of sensory neurons restores PER response to tarsal sucrose stimulation. Similar override of PER habituation can also be induced by brief thermogenetic activation of a population of tyrosine hydroxylase (TH)-positive neurons, a subset of which send projections to the subesophageal zone (SEZ). Significantly, sensory-neuron induced habituation override requires transmitter release from these TH-positive cells. Treatments that cause override specifically influence the habituated state, with no effect on the naive sucrose response across a range of concentrations. Taken together with other findings, these observations in female flies are consistent with a model in which novel taste stimuli trigger activity in dopaminergic neurons which, directly or indirectly, inhibit GABAergic cells that drive PER habituation. The implications of these findings for general mechanisms of attentional and sensory override of habituation are discussed.SIGNIFICANCE STATEMENT Habituation can be overcome when a new context requires an enhanced response to a familiar stimulus. However, the underlying mechanisms remain incompletely understood. Previous studies have provided evidence that habituation of the sucrose-induced proboscis extension reflex (PER) in Drosophila occurs through potentiation of inhibition onto the PER pathway. This work defines controlled protocols for override of PER habituation and uses them to outline the underlying circuit mechanisms. The results presented support a model in which novel taste stimuli cause dishabituation by activating a subset of tyrosine hydroxylase (TH)-expressing neurons that inhibit GABAergic neurons whose potentiation underlies PER habituation. At a general level, these findings further highlight a central role for inhibition and disinhibition in the control of behavioral flexibility.