An analysis of reinstatement after extinction of a conditioned taste aversion.

Taste aversion learning has sometimes been considered a specialized form of learning. In several other conditioning preparations, after a conditioned stimulus (CS) is conditioned and extinguished, reexposure to the unconditioned stimulus (US) by itself can reinstate the extinguished conditioned response. Reinstatement has been widely studied in fear and appetitive Pavlovian conditioning, as well as operant conditioning, but its status in taste aversion learning is more controversial. Six taste-aversion experiments with rats therefore sought to discover conditions that might encourage it there. The results often yielded little to no evidence of reinstatement, and we also found no evidence of concurrent recovery, a related phenomenon in which responding to a CS that has been conditioned and extinguished is restored if a second CS is separately conditioned. However, a key result was that reinstatement occurred when the conditioning procedure involved multiple closely spaced conditioning trials that could have allowed the animal to learn that a US presentation signaled or set the occasion for another trial with a US. Such a mechanism is precluded in many taste aversion experiments because they often use very few conditioning trials. Overall, the results suggest that taste aversion learning is experimentally unique, though not necessarily biologically or evolutionarily unique. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Addition of low sodium does not increase sensitivity to glucose in wild-type mice, or lead to partial glucose taste detection in T1R3 knock-out mice.

The sodium glucose cotransporter 1 (SGLT1) has been proposed as a non-T1R glucosensor contributing to glucose taste. Studies have shown that the addition of NaCl at very weak concentrations to a glucose stimulus can enhance signaling in the gustatory nerves of mice and significantly lower glucose detection thresholds in humans. Here, we trained mice with (wild-type; WT) and without (knockout; KO) a functioning T1R3 subunit on a two-response operant detection task to differentially respond to the presence or absence of a taste stimulus immediately after sampling. After extensive training (∼40 sessions), KO mice were unable to reliably discriminate 2 M glucose+0.01 M NaCl from 0.01 M NaCl alone, but all WT mice could. We then tested WT mice on a descending array of glucose concentrations (2.0-0.03 M) with the addition of 0.01 M NaCl vs. 0.01 M NaCl alone. The concentration series was then repeated with glucose alone vs. water. We found no psychophysical evidence of a non-T1R taste transduction pathway involved in the detection of glucose. The addition of NaCl to glucose did not lower taste detection thresholds in WT mice, nor did it render the stimulus detectable to KO mice, even at 2 M. The proposed pathway must contribute to functions other than sensory-discriminative detection, at least when tested under these conditions. Detection thresholds were also derived for fructose and found to be 1/3 log10 lower than for glucose, but highly correlated (r = 0.88) between the two sugars, suggesting that sensitivity to these stimuli in this task was based on a similar neural process.

Does presbygeusia really exist? An updated narrative review.

This review critically assessed the existence of presbygeusia, i.e., the impairment in taste perception occurring in the elderly, as a natural part of the aging process and its potential clinical implications. Several factors might contribute to age-related taste alterations (TAs), including structural changes in taste buds, alterations in saliva composition, central nervous system changes, and oral microbiota dysbiosis. A comprehensive literature review was conducted to disentangle the effects of age from those of the several age-related diseases or conditions promoting TAs. Most of the included studies reported TAs in healthy elderly people, suggesting that presbygeusia is a relatively frequent condition associated with age-related changes in the absence of pathological conditions. However, the impact of TAs on dietary preferences and food choices among the elderly seems to be less relevant when compared to other factors, such as cultural, psychological, and social influences. In conclusion, presbygeusia exists even in the absence of comorbidities or drug side effects, but its impact on dietary choices in the elderly is likely modest.

Bitter taste receptor activation by cholesterol and an intracellular tastant.

Bitter taste sensing is mediated by type 2 taste receptors (TAS2Rs (also known as T2Rs)), which represent a distinct class of G-protein-coupled receptors1. Among the 26 members of the TAS2Rs, TAS2R14 is highly expressed in extraoral tissues and mediates the responses to more than 100 structurally diverse tastants2-6, although the molecular mechanisms for recognizing diverse chemicals and initiating cellular signalling are still poorly understood. Here we report two cryo-electron microscopy structures for TAS2R14 complexed with Ggust (also known as gustducin) and Gi1. Both structures have an orthosteric binding pocket occupied by endogenous cholesterol as well as an intracellular allosteric site bound by the bitter tastant cmpd28.1, including a direct interaction with the α5 helix of Ggust and Gi1. Computational and biochemical studies validate both ligand interactions. Our functional analysis identified cholesterol as an orthosteric agonist and the bitter tastant cmpd28.1 as a positive allosteric modulator with direct agonist activity at TAS2R14. Moreover, the orthosteric pocket is connected to the allosteric site via an elongated cavity, which has a hydrophobic core rich in aromatic residues. Our findings provide insights into the ligand recognition of bitter taste receptors and suggest activities of TAS2R14 beyond bitter taste perception via intracellular allosteric tastants.

Evolutionary origins of bitter taste receptors in jawed vertebrates.

Taste is a sense that detects information about nutrients and toxins in foods. Of the five basic taste qualities, bitterness is associated with the detection of potentially harmful substances like plant alkaloids. In bony vertebrates, type 2 taste receptors (T2Rs), which are G-protein-coupled receptors (GPCRs), act as bitter taste receptors1,2. In vertebrates, six GPCR gene families are described as chemosensory receptor genes, encoding taste receptor families (T1Rs and T2Rs) and olfactory receptor families (ORs, V1Rs, V2Rs, and TAARs). These families of receptors have been found in all major jawed vertebrate lineages, except for the T2Rs, which are confined to bony vertebrates3. Therefore, T2Rs are believed to have emerged later than the other chemosensory receptor genes in the bony vertebrate lineage. So far, only the genomes of two cartilaginous fish species have been mined for TAS2R genes, which encode T2Rs4. Here, we identified novel T2Rs in elasmobranchs, namely selachimorphs (sharks) and batoids (rays, skates, and their close relatives) by an exhaustive search covering diverse cartilaginous fishes. Using functional and mRNA expression analyses, we demonstrate that their T2Rs are expressed in the oral taste buds and contribute to the detection of bitter compounds. This finding indicates the early origin of T2Rs in the common ancestor of jawed vertebrates.

Long-Term Taste and Smell Outcomes After COVID-19.

Importance: Self-report surveys suggest that long-lasting taste deficits may occur after SARS-CoV-2 infection, influencing nutrition, safety, and quality of life. However, self-reports of taste dysfunction are inaccurate, commonly reflecting deficits due to olfactory not taste system pathology; hence, quantitative testing is needed to verify the association of post-COVID-19 condition with taste function. Objective: To use well-validated self-administered psychophysical tests to investigate the association of COVID-19 with long-term outcomes in taste and smell function. Design, Setting, and Participants: This nationwide cross-sectional study included individuals with and without a prior history of COVID-19 recruited from February 2020 to August 2023 from a social media website (Reddit) and bulletin board advertisements. In the COVID-19 cohort, there was a mean of 395 days (95% CI, 363-425 days) between diagnosis and testing. Exposure: History of COVID-19. Main Outcomes and Measures: The 53-item Waterless Empirical Taste Test (WETT) and 40-item University of Pennsylvania Smell Identification Test (UPSIT) were used to assess taste and smell function. Total WETT and UPSIT scores and WETT subtest scores of sucrose, citric acid, sodium chloride, caffeine, and monosodium glutamate were assessed for groups with and without a COVID-19 history. The association of COVID-19 with taste and smell outcomes was assessed using analysis of covariance, χ2, and Fisher exact probability tests. Results: Tests were completed by 340 individuals with prior COVID-19 (128 males [37.6%] and 212 females [62.4%]; mean [SD] age, 39.04 [14.35] years) and 434 individuals with no such history (154 males [35.5%] and 280 females [64.5%]; mean (SD) age, 39.99 [15.61] years). Taste scores did not differ between individuals with and without previous COVID-19 (total WETT age- and sex-adjusted mean score, 33.41 [95% CI, 32.37-34.45] vs 33.46 [95% CI, 32.54-34.38]; P = .94). In contrast, UPSIT scores were lower in the group with previous COVID-19 than the group without previous COVID-19 (mean score, 34.39 [95% CI, 33.86-34.92] vs 35.86 [95% CI, 35.39-36.33]; P < .001]); 103 individuals with prior COVID-19 (30.3%) and 91 individuals without prior COVID-19 (21.0%) had some degree of dysfunction (odds ratio, 1.64 [95% CI, 1.18-2.27]). The SARS-CoV-2 variant present at the time of infection was associated with smell outcomes; individuals with original untyped and Alpha variant infections exhibited more loss than those with other variant infections; for example, total to severe loss occurred in 10 of 42 individuals with Alpha variant infections (23.8%) and 7 of 52 individuals with original variant infections (13.5%) compared with 12 of 434 individuals with no COVID-19 history (2.8%) (P < .001 for all). Conclusions and Relevance: In this study, taste dysfunction as measured objectively was absent 1 year after exposure to COVID-19 while some smell loss remained in nearly one-third of individuals with this exposure, likely explaining taste complaints of many individuals with post-COVID-19 condition. Infection with earlier untyped and Alpha variants was associated with the greatest degree of smell loss.

Bitter Taste Receptor T2R14 and Autophagy Flux in Gingival Epithelial Cells.

Macroautophagy (hereafter autophagy) is a lysosomal degradation pathway that functions in nutrient recycling and as a mechanism of innate immunity. Previously, we reported a novel host-bacteria interaction between cariogenic S. mutans and bitter taste receptor (T2R14) in gingival epithelial cells (GECs), leading to an innate immune response. Further, S. mutans might be using the host immune system to inhibit other Gram-positive bacteria, such as S. aureus. To determine whether these bacteria exploit the autophagic machinery of GEC, it is first necessary to evaluate the role of T2R14 in modulating autophagic flux. So far, the role of T2R14 in the regulation of autophagy is not well characterized. Therefore, in this study, for the first time, we report that T2R14 downregulates autophagy flux in GECs, and T2R14 knockout increases acidic vacuoles. However, the treatments of GEC WT with a T2R14 agonist and antagonist did not lead to a significant change in acidic vacuole formation. Transmission electron microscopy morphometric results also suggested an increased number of autophagic vesicles in T2R14-knockout GEC. Further, our results suggest that S. mutans competence stimulating peptide CSP-1 showed robust intracellular calcium release and this effect is both T2R14- and autophagy protein 7-dependent. In this study, we provide the first evidence that T2R14 modulates autophagy flux in GEC. The results of the current study could help in identifying the impact of T2R in regulation of the immuno-microenvironment of GEC and subsequently oral health.

The pharyngeal taste organ of a blood-feeding insect functions in food recognition.

BACKGROUND: Obligate blood-feeding insects obtain the nutrients and water necessary to ensure survival from the vertebrate blood. The internal taste sensilla, situated in the pharynx, evaluate the suitability of the ingested food. Here, through multiple approaches, we characterized the pharyngeal organ (PO) of the hematophagous kissing bug Rhodnius prolixus to determine its role in food assessment. The PO, located antero-dorsally in the pharynx, comprises eight taste sensilla that become bathed with the incoming blood. RESULTS: We showed that these taste sensilla house gustatory receptor neurons projecting their axons through the labral nerves to reach the subesophageal zone in the brain. We found that these neurons are electrically activated by relevant appetitive and aversive gustatory stimuli such as NaCl, ATP, and caffeine. Using RNA-Seq, we examined the expression of sensory-related gene families in the PO. We identified gustatory receptors, ionotropic receptors, transient receptor potential channels, pickpocket channels, opsins, takeouts, neuropeptide precursors, neuropeptide receptors, and biogenic amine receptors. RNA interference assays demonstrated that the salt-related pickpocket channel Rproppk014276 is required during feeding of an appetitive solution of NaCl and ATP. CONCLUSIONS: We provide evidence of the role of the pharyngeal organ in food evaluation. This work shows a comprehensive characterization of a pharyngeal taste organ in a hematophagous insect.

[Research progress in functional regeneration methods and mechanisms of taste buds].

Gustation is one of the most important human senses. Taste dysfunctions, which may be due to aging, tongue cancer surgery, radiotherapy and chemotherapy, affect life quality. That is why the need for taste bud regeneration has received more attention. At present, research on development and renewal of taste cells provides a basis for taste bud regeneration; molecular mechanisms related to taste bud regeneration are being continuously uncoverd, aiding in the identification of more accurate targets for therapy. New methods such as nerve regeneration, tissue engineering, and cytokine therapy have emerged. The author reviews the mechanism and the latest methods of taste bud regeneration of lingual epithelium, aiming to open new horizions for the prevention and treatment of gustatory diseases, and provide theoretical references for its regeneration.

Neuroscience of taste: unlocking the human taste code.

Since antiquity human taste has been divided into 4-5 taste qualities. We realized in the early 1970s that taste qualities vary between species and that the sense of taste in species closer to humans such as primates should show a higher fidelity to human taste qualities than non-primates (Brouwer et al. in J Physiol 337:240, 1983). Here we present summary results of behavioral and single taste fiber recordings from the distant South American marmoset, through the Old World rhesus monkey to chimpanzee, the phylogenetically closest species to humans. Our data show that in these species taste is transmitted in labelled-lines to the CNS, so that when receptors on taste bud cells are stimulated, the cell sends action potentials through single taste nerve fibers to the CNS where they create taste, whose quality depends on the cortical area stimulated. In human, the taste qualites include, but are perhaps not limited to sweet, sour, salty, bitter and umami. Stimulation of cortical taste areas combined with inputs from internal organs, olfaction, vision, memory etc. leads to a choice to accept or reject intake of a compound. The labelled-line organization of taste is another example of Müller's law of specific nerve energy, joining other somatic senses such as vision (Sperry in J Neurophysiol 8:15-28, 1945), olfaction (Ngai et al. in Cell 72:657-666, 1993), touch, temperature and pain to mention a few.

Chemosensory changes during chemotherapy.

BACKGROUND: Chemosensory changes that occur during chemotherapy can significantly impact food enjoyment, quality of life and recovery. AIM: To investigate chemosensory changes reported by oncology patients during chemotherapy. METHODS: A mixed-method cross-sectional study design was used to explore 100 cancer patients' experiences of chemosensory changes during chemotherapy. All patients completed a questionnaire assessing their taste and smell preferences. A purposive sample of 30 patients underwent a semi-structured interview to elicit their thoughts on their experienced chemosensory changes. Descriptive statistics and themes were examined. FINDINGS: The mean age of the sample was 50.56 years, and the majority of participants were female. The most stated taste alteration was bitter, while altered food preferences were also commonly experienced. Furthermore, most patients experienced unpleasant odours around food, while some experienced these odours even when food was not present. Overall, five themes were identified: changes in taste, changes in smell, changes in social life, altered comfort and food preferences. CONCLUSION: Chemosensory changes related to cancer and its treatment impact a person's nutrient intake, food-related behaviours, quality of life and treatment response. Patients who experience chemotherapy-associated chemosensory changes require specialised nutritional therapy to increase their eating-related pleasure. As part of the nutritional assessment, chemosensory alterations should be evaluated regularly.

Palatability attributed to alcohol and alcohol-paired flavors.

The orosensory features of alcoholic drinks are potent relapse triggers because they acquire incentive properties during consumption, including enhanced palatability. Whether mice similarly perceive alcoholic drinks to be more palatable after repeated consumption is complicated by reports showing that alcohol elicits aversive taste reactivity responses and conditions flavor avoidance. Here, by analyzing the microstructure of alcohol consumption, we report a gradual increase in lick bout duration relative to water that is partially maintained by an alcohol-paired flavor in extinction. We interpret lick bout duration to reflect an increase in the palatability alcohol and an alcohol-paired flavor. This finding demonstrates that bout duration is amenable to Pavlovian conditioning and highlights the importance of considering the microstructure of alcohol consumption in preclinical models of alcohol misuse.

Development of Taste Sensor with Lipid/Polymer Membranes for Detection of Umami Substances Using Surface Modification.

A taste sensor employs various lipid/polymer membranes with specific physicochemical properties for taste classification and evaluation. However, phosphoric acid di(2-ethylhexyl) ester (PAEE), employed as one of the lipids for the taste sensors, exhibits insufficient selectivity for umami substances. The pH of sample solutions impacts the dissociation of lipids to influence the membrane potential, and the response to astringent substances makes accurate measurement of umami taste difficult. This study aims to develop a novel taste sensor for detecting umami substances like monosodium L-glutamate (MSG) through surface modification, i.e., a methodology previously applied to taste sensors for non-charged bitter substance measurement. Four kinds of modifiers were tested as membrane-modifying materials. By comparing the results obtained from these modifiers, the modifier structure suitable for measuring umami substances was identified. The findings revealed that the presence of carboxyl groups at para-position of the benzene ring, as well as intramolecular H-bonds between the carboxyl group and hydroxyl group, significantly affect the effectiveness of a modifier in the umami substance measurement. The taste sensor treated with this type of modifier showed excellent selectivity for umami substances.

Structural basis for sugar perception by Drosophila gustatory receptors.

Insects rely on a family of seven transmembrane proteins called gustatory receptors (GRs) to encode different taste modalities, such as sweet and bitter. We report structures of Drosophila sweet taste receptors GR43a and GR64a in the apo and sugar-bound states. Both GRs form tetrameric sugar-gated cation channels composed of one central pore domain (PD) and four peripheral ligand-binding domains (LBDs). Whereas GR43a is specifically activated by the monosaccharide fructose that binds to a narrow pocket in LBDs, disaccharides sucrose and maltose selectively activate GR64a by binding to a larger and flatter pocket in LBDs. Sugar binding to LBDs induces local conformational changes, which are subsequently transferred to the PD to cause channel opening. Our studies reveal a structural basis for sugar recognition and activation of GRs.

What are olfaction and gustation, and do all animals have them?

Different animals have distinctive anatomical and physiological properties to their chemical senses that enhance detection and discrimination of relevant chemical cues. Humans and other vertebrates are recognized as having 2 main chemical senses, olfaction and gustation, distinguished from each other by their evolutionarily conserved neuroanatomical organization. This distinction between olfaction and gustation in vertebrates is not based on the medium in which they live because the most ancestral and numerous vertebrates, the fishes, live in an aquatic habitat and thus both olfaction and gustation occur in water and both can be of high sensitivity. The terms olfaction and gustation have also often been applied to the invertebrates, though not based on homology. Consequently, any similarities between olfaction and gustation in the vertebrates and invertebrates have resulted from convergent adaptations or shared constraints during evolution. The untidiness of assigning olfaction and gustation to invertebrates has led some to recommend abandoning the use of these terms and instead unifying them and others into a single category-chemical sense. In our essay, we compare the nature of the chemical senses of diverse animal types and consider their designation as olfaction, oral gustation, extra-oral gustation, or simply chemoreception. Properties that we have found useful in categorizing chemical senses of vertebrates and invertebrates include the nature of peripheral sensory cells, organization of the neuropil in the processing centers, molecular receptor specificity, and function.

Lingual Taste Nerve Transection Alters Food Selection, Relative Macronutrient Intake, and Meal Patterns in Rats Consuming a Cafeteria Diet without Changing Total Energy Intake.

The control of ingestive behavior is complex and involves input from many different sources, including the gustatory system. Signals transmitted via the taste nerves trigger responses that promote or discourage ingestion. The lingual taste nerves innervate 70% of taste buds, yet their role in the control of food selection and intake remarkably remains relatively underinvestigated. Here we used our custom five-item Food Choice Monitor to compare postsurgical behavioral responses to chow and a five-choice cafeteria diet (CAF) between male rats that had sham surgery (SHAM) or histologically verified transection of the chorda tympani and glossopharyngeal nerves (2NX). Compared with SHAM rats, 2NX rats ate significantly more of the high-fat CAF foods. The altered food choices led to dramatically increased fat intake and substantially reduced carbohydrate intake by 2NX vs SHAM rats. Furthermore, whether offered chow or CAF, 2NX rats ate fewer, larger meals each day. Eating rates implied that, compared with SHAM, 2NX rats were equally motivated to consume CAF but less motivated to eat chow. Even with these differences, energy intake and weight gain trajectories remained similar between SHAM and 2NX rats. Although some rats experienced CAF before surgery, contrary to our expectations, the effects of prior CAF experience on postsurgical eating were minimal. In conclusion, although total energy intake was unaffected, our results clearly indicate that information from one or both lingual taste nerves has a critical role in food selection, regulation of macronutrient intake, and meal termination but not long-term energy balance.

Sniffing out meaning: Chemosensory and semantic neural network changes in sommeliers.

Wine tasting is a very complex process that integrates a combination of sensation, language, and memory. Taste and smell provide perceptual information that, together with the semantic narrative that converts flavor into words, seem to be processed differently between sommeliers and naïve wine consumers. We investigate whether sommeliers' wine experience shapes only chemosensory processing, as has been previously demonstrated, or if it also modulates the way in which the taste and olfactory circuits interact with the semantic network. Combining diffusion-weighted images and fMRI (activation and connectivity) we investigated whether brain response to tasting wine differs between sommeliers and nonexperts (1) in the sensory neural circuits representing flavor and/or (2) in the neural circuits for language and memory. We demonstrate that training in wine tasting shapes the microstructure of the left and right superior longitudinal fasciculus. Using mediation analysis, we showed that the experience modulates the relationship between fractional anisotropy and behavior: the higher the fractional anisotropy the higher the capacity to recognize wine complexity. In addition, we found functional differences between sommeliers and naïve consumers affecting the flavor sensory circuit, but also regions involved in semantic operations. The former reflects a capacity for differential sensory processing, while the latter reflects sommeliers' ability to attend to relevant sensory inputs and translate them into complex verbal descriptions. The enhanced synchronization between these apparently independent circuits suggests that sommeliers integrated these descriptions with previous semantic knowledge to optimize their capacity to distinguish between subtle differences in the qualitative character of the wine.

Novel kokumi peptides from yeast extract and their taste mechanism via an in silico study.

Yeast extract, a widely utilized natural substance in the food industry and biopharmaceutical field, holds significant potential for flavor enhancement. Kokumi peptides within yeast extracts were isolated through ultrafiltration and gel chromatography, followed by identification using liquid chromatography tandem mass spectrometry (LC-MS/MS). Two peptides, IQGFK and EDFFVR, were identified and synthesized using solid-phase methods based on molecular docking outcomes. Sensory evaluations and electronic tongue analyses conducted with chicken broth solutions revealed taste thresholds of 0.12 mmol L-1 for IQGFK and 0.16 mmol L-1 for EDFFVR, respectively, and both peptides exhibited kokumi properties. Additionally, through molecular dynamics simulations, the binding mechanisms between these peptides and the calcium-sensing receptor (CaSR) were explored. The findings indicated stable binding of both peptides to the receptor. IQGFK primarily interacted through electrostatic interactions, with key binding sites including Asp275, Asn102, Pro274, Trp70, Tyr218, and Ser147. EDFFVR mainly engaged via van der Waals energy and polar solvation free energy, with key binding sites being Asp275, Ile416, Pro274, Arg66, Ala298, and Tyr218. This suggests that both peptides can activate the CaSR, thereby inducing kokumi activity. This study provides a theoretical foundation and reference for the screening and identification of kokumi peptides, successfully uncovering two novel kokumi peptides derived from yeast extract.

Molecular basis of host plant recognition by silkworm larvae.

Herbivorous insects can identify their host plants by sensing plant secondary metabolites as chemical cues. We previously reported the two-factor host acceptance system of the silkworm Bombyx mori larvae. The chemosensory neurons in the maxillary palp (MP) of the larvae detect mulberry secondary metabolites, chlorogenic acid (CGA), and isoquercetin (ISQ), with ultrahigh sensitivity, for host plant recognition and feeding initiation. Nevertheless, the molecular basis for the ultrasensitive sensing of these compounds remains unknown. In this study, we demonstrated that two gustatory receptors (Grs), BmGr6 and BmGr9, are responsible for sensing the mulberry compounds with attomolar sensitivity for host plant recognition by silkworm larvae. Calcium imaging assay using cultured cells expressing the silkworm putative sugar receptors (BmGr4-10) revealed that BmGr6 and BmGr9 serve as receptors for CGA and ISQ with attomolar sensitivity in human embryonic kidney 293T cells. CRISPR/Cas9-mediated knockout (KO) of BmGr6 and BmGr9 resulted in a low probability of making a test bite of the mulberry leaves, suggesting that they lost the ability to recognize host leaves. Electrophysiological recordings showed that the loss of host recognition ability in the Gr-KO strains was due to a drastic decrease in MP sensitivity toward ISQ in BmGr6-KO larvae and toward CGA and ISQ in BmGr9-KO larvae. Our findings have revealed that the two Grs, previously considered to be sugar receptors, are molecules responsible for detecting plant phenolics in host plant recognition.