Search

Studies on taste bud cells and brain stem relay nuclei suggest that alternative pathways convey information regarding different taste qualities. Building on the hypothesis that amiloride (epithelial Na channel antagonist)-sensitive neurons respond to palatable salt (low-concentration) and amiloride-insensitive neurons respond to aversive salt (high-concentration), we investigated the histological distribution of taste-sensitive neurons in the rostral nucleus of the solitary tract in rats and their NaCl and amiloride sensitivities. We recorded neuronal activity in extracellular single units using multi-barrel glass micropipettes and reconstructed their locations on the rostrocaudal and mediolateral axes. Seventy-three taste-sensitive neurons were categorized into the best-taste category. The amiloride sensitivities of the 31 neurons were examined for 0.1, 0.2, 0.4, and 0.8 M NaCl. The neuronal distribution of amiloride-sensitive neurons was located in the lateral region, while amiloride-insensitive neurons were located in the medial region. The amiloride-sensitive neurons responded to low salt concentrations, signaling the NaCl levels required by body fluids. Amiloride-insensitive neurons were silent at low salt concentrations but may function as warning signals for high salt concentrations. Low-threshold and/or high-response neurons were located in the rostrolateral region. In contrast, high-threshold and/or low-response neurons were located in the caudal-medial region., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

The peripheral taste system is more complex than previously thought. The novel taste-signaling proteins TRPM4 and PLCβ3 appear to function in normal taste responding as part of Type II taste cell signaling or as part of a broadly responsive (BR) taste cell that can respond to some or all classes of tastants. This work begins to disentangle the roles of intracellular components found in Type II taste cells (TRPM5, TRPM4, and IP3R3) or the BR taste cells (PLCβ3 and TRPM4) in driving behavioral responses to various saccharides and other sweeteners in brief-access taste tests. We found that TRPM4, TRPM5, TRPM4/5, and IP3R3 knockout (KO) mice show blunted or abolished responding to all stimuli compared with wild-type. IP3R3 KO mice did, however, lick more for glucose than fructose following extensive experience with the 2 sugars. PLCβ3 KO mice were largely unresponsive to all stimuli except they showed normal concentration-dependent responding to glucose. The results show that key intracellular signaling proteins associated with Type II and BR taste cells are mutually required for taste-driven responses to a wide range of sweet and carbohydrate stimuli, except glucose. This confirms and extends a previous finding demonstrating that Type II and BR cells are both necessary for taste-driven licking to sucrose. Glucose appears to engage unique intracellular taste-signaling mechanisms, which remain to be fully elucidated., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

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., (© The Author(s) 2024. Published by Oxford University Press.)

Taste receptor cells are morphologically classified as types II and III. Type II cells form a unique type of synapses referred to as channel synapses where calcium homeostasis modulator 1 (CALHM1) together with CALHM3 forms voltage-gated channels that release the neurotransmitter, adenosine triphosphate (ATP). To validate the proposed structural model of channel synapses, the ultrastructural localization of CALHM1 in type II cells of both fungiform and circumvallate taste buds was examined. A monoclonal antibody against CALHM1 was developed and its localization was evaluated via immunofluorescence and immunoelectron microscopy using the immunogold-silver labeling technique. CALHM1 was detected as puncta using immunofluorescence and along the presynaptic membrane of channel synapses facing atypical mitochondria, which provide ATP, by immunoelectron microscopy. In addition, it was detected along the plasma membrane lined by subsurface cisternae at sites apposed to afferent nerve fibers. Our results support the validity of a previously proposed structural model for channel synapses and provide insights into the function of subsurface cisternae whose function in taste receptor cells is unknown. We also examined the localization of CALHM1 in hybrid synapses of type III cells, which are conventional chemical synapses accompanied by mitochondria similar to atypical mitochondria of channel synapses. CALHM1 was not detected in the six hybrid synapses examined using immunoelectron microscopy. We further performed double immunolabeling for CALHM1 and Bassoon, which is detected as puncta corresponding to conventional vesicular synapses in type III cells. Our observations suggest that at least some, and probably most, hybrid synapses are not accompanied by CALHM1., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Mammalian taste buds are highly regenerative and can restore themselves after normal wear and tear of the lingual epithelium or following physical and chemical insults, including burns, chemotherapy, and nerve injury. This is due to the continual proliferation, differentiation, and maturation of taste progenitor cells, which then must reconnect with peripheral gustatory neurons to relay taste signals to the brain. The turnover and re-establishment of peripheral taste synapses are vital to maintain this complex sensory system. Over the past several decades, the signal transduction and neurotransmitter release mechanisms within taste cells have been well delineated. However, the complex dynamics between synaptic partners in the tongue (taste cell and gustatory neuron) are only partially understood. In this review, we highlight recent findings that have improved our understanding of the mechanisms governing connectivity and signaling within the taste bud and the still-unresolved questions regarding the complex interactions between taste cells and gustatory neurons., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Prebiotic oligosaccharides are naturally occurring nondigestible carbohydrates with demonstrated health benefits. They are also a chemically diverse class of nutrients, offering an opportunity to investigate the impact of molecular structure on oligosaccharide taste perception. Accordingly, a relevant question is whether these compounds are detected by the human gustatory system, and if so, whether they elicit sweet or "starchy" taste. Here, in 3 psychophysical experiments, we investigated the taste perception of 3 commercially popular prebiotics [fructooligosaccharides (FOS), galactooligosaccharides (GOS), xylooligosaccharides (XOS)] in highly pure form. Each of these classes of prebiotics differs in the type of glycosyl residue, and position and type of bond between those residues. In experiments I and II, participants were asked to discriminate a total of 9 stimuli [FOS, GOS, XOS; degree of polymerization (DP) of 2, 3, 4] prepared at 75 mM in the presence and absence of lactisole, a sweet receptor antagonist. We found that all 9 compounds were detectable (P < 0.05). We also found that GOS and XOS DP 4 were discriminable even with lactisole, suggesting that their detection was not via the canonical sweet receptor. Accordingly, in experiment III, the taste of GOS and XOS DP 4 were directly compared with that of MOS (maltooligosaccharides) DP 4-6, which has been reported to elicit "starchy" taste. We found that GOS and MOS were perceived similarly although narrowly discriminable, while XOS was easily discriminable from both GOS and MOS. The current findings suggest that the molecular structure of oligosaccharides impacts their taste perception in humans., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Animals use sour taste to avoid spoiled food and to choose foods containing vitamins and minerals. To investigate the response to sour taste substances during vitamin C (ascorbic acid; AA) deficiency, we conducted behavioral, neural, anatomical, and molecular biological experiments with osteogenic disorder Shionogi/Shi Jcl-od/od rats, which lack the ability to synthesize AA. Rats had higher 3 mM citric acid and 10 mM AA preference scores when AA-deficient than when replete. Licking rates for sour taste solutions [AA, citric acid, acetic acid, tartaric acid, and HCl] were significantly increased during AA deficiency relative to pre- and postdeficiency. Chorda tympani nerve recordings were conducted to evaluate organic acid taste responses in the AA-deficient and replete rats. Nerve responses to citric acid, acetic acid, and tartaric acid were significantly diminished in AA-deficient rats relative to replete controls. There was no significant difference in the number of fungiform papillae taste buds per unit area in the AA-deficient rats relative to the replete rats. However, mRNA expression levels of Gnat3 (NM&#95;173139.1), Trpm5 (NM&#95;001191896.1), Tas1r1 (NM&#95;053305.1), Car4 (NM&#95;019174.3), and Gad1 (NM&#95;017007.1) in fungiform papillae taste bud cells from AA-deficient rats were significantly lower than those in replete rats. Our data suggest that AA deficiency decreases avoidance of acids and reduces chorda tympani nerve responses to acids. AA deficiency downregulates some taste-related genes in fungiform papillae taste bud cells. However, the results also reveal that the mRNA expression of some putative sour taste receptors in fungiform papillae taste bud cells is not affected by AA deficiency., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Most patients report "taste" changes after undergoing metabolic surgeries. Yet, most studies that used validated sensory evaluation techniques, including ours, found no changes in perceived taste intensity from before to after surgery. However, we assessed participants with pure gustatory stimuli and after an overnight fast, which raises questions about whether patients' self-reported "taste" changes are due to conflating changes in retronasal smell/"flavor" with taste changes or whether they only manifest during the fed state. To investigate this, we conducted a cross-sectional study comparing sensory responses in women who underwent metabolic surgery 2 to 6 yr ago (n = 15) with 2 nonoperated control groups: one with a body mass index (BMI) equivalent (n = 15) and one with a healthy BMI (n = 15). Participants attended 2 sessions, one fed and one fasted. Using a sip-and-spit method, women tasted liquid samples containing gustatory and olfactory stimuli and puddings with varying fat content with and without nose clips. They used separate general labeled magnitude scales to rate their perceived intensity of taste, smell, flavor, and liking. Mixed ANOVAs indicated that the surgery and BMI equivalent groups rated retronasal smell intensity of coffee stronger than the healthy BMI group (P ≤ 0.015). However, there were no differences in taste/flavor intensity or liking ratings among groups. Additionally, feeding conditions did not significantly affect perceived intensity ratings. Our findings suggest that changes in the sensory-discriminatory component of taste or taste-odor interactions are not significant contributors to dietary modifications following metabolic surgery., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

The sweet taste receptor (STR) is a G protein-coupled receptor (GPCR) responsible for mediating cellular responses to sweet stimuli. Early evidence suggests that elements of the STR signaling system are present beyond the tongue in metabolically active tissues, where it may act as an extraoral glucose sensor. This study aimed to delineate expression of the STR in extraoral tissues using publicly available RNA-sequencing repositories. Gene expression data was mined for all genes implicated in the structure and function of the STR, and control genes including highly expressed metabolic genes in relevant tissues, other GPCRs and effector G proteins with physiological roles in metabolism, and other GPCRs with expression exclusively outside the metabolic tissues. Since the physiological role of the STR in extraoral tissues is likely related to glucose sensing, expression was then examined in diseases related to glucose-sensing impairment such as type 2 diabetes. An aggregate co-expression network was then generated to precisely determine co-expression patterns among the STR genes in these tissues. We found that STR gene expression was negligible in human pancreatic and adipose tissues, and low in intestinal tissue. Genes encoding the STR did not show significant co-expression or connectivity with other functional genes in these tissues. In addition, STR expression was higher in mouse pancreatic and adipose tissues, and equivalent to human in intestinal tissue. Our results suggest that STR expression in mice is not representative of expression in humans, and the receptor is unlikely to be a promising extraoral target in human cardiometabolic disease., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The senses of taste and smell detect overlapping sets of chemical compounds in fish, e.g. amino acids are detected by both senses. However, so far taste and smell organs appeared morphologically to be very distinct, with a specialized olfactory epithelium for detection of odors and taste buds located in the oral cavity and lip for detection of tastants. Here, we report dense clusters of cells expressing T1R and T2R receptors as well as their signal transduction molecule PLCβ2 in nostrils of zebrafish, i.e. on the entrance funnel through which odor molecules must pass to be detected by olfactory sensory neurons. Quantitative evaluation shows the density of these chemosensory cells in the nostrils to be as high or higher than that in the established taste organs oral cavity and lower lip. Hydrodynamic flow is maximal at the nostril rim enabling high throughput chemosensation in this organ. Taken together, our results suggest a sentinel function for these chemosensory cells in the nostril., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Sensory cells that specialize in transducing olfactory and gustatory stimuli are renewed throughout life and can regenerate after injury unlike their counterparts in the mammalian retina and auditory epithelium. This uncommon capacity for regeneration offers an opportunity to understand mechanisms that promote the recovery of sensory function after taste and smell loss. Immune responses appear to influence degeneration and later regeneration of olfactory sensory neurons and taste receptor cells. Here we review surgical, chemical, and inflammatory injury models and evidence that immune responses promote or deter chemosensory cell regeneration. Macrophage and neutrophil responses to chemosensory receptor injury have been the most widely studied without consensus on their net effects on regeneration. We discuss possible technical and biological reasons for the discrepancy, such as the difference between peripheral and central structures, and suggest directions for progress in understanding immune regulation of chemosensory regeneration. Our mechanistic understanding of immune-chemosensory cell interactions must be expanded before therapies can be developed for recovering the sensation of taste and smell after head injury from traumatic nerve damage and infection. Chemosensory loss leads to decreased quality of life, depression, nutritional challenges, and exposure to environmental dangers highlighting the need for further studies in this area., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The central gustatory pathway encompasses multiple subcortical and cortical regions whose neural functional connectivity can be modulated by taste stimulation. While gustatory perception has been previously linked to sex, whether and how the gustatory network differently responds to basic tastes between men and women is unclear. Here, we defined the regions of the central gustatory network by a meta-analysis of 35 fMRI taste activation studies and then analyzed the taste-evoked functional connectivity between these regions in 44 subjects (19 women) in a separate 3 Tesla activation study where sweet and bitter solutions, at five concentrations each, were administered during scanning. From the meta-analysis, a network model was set up, including bilateral anterior, middle and inferior insula, thalamus, precentral gyrus, left amygdala, caudate and dorsolateral prefrontal cortex. Higher functional connectivity than in women was observed in men between the right middle insula and bilateral thalami for bitter taste. Men exhibited higher connectivity than women at low bitter concentrations and middle-high sweet concentrations between bilateral thalamus and insula. A graph-based analysis expressed similar results in terms of nodal characteristics of strength and centrality. Our findings add new insights into the mechanisms of taste processing by highlighting sex differences in the functional connectivity of the gustatory network as modulated by the perception of sweet and bitter tastes. These results shed more light on the neural origin of sex-related differences in gustatory perception and may guide future research on the pathophysiology of taste perception in humans., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Controversy and misunderstanding surround the role of feeding specialization in taste receptor loss in vertebrates. We refined and tested the hypothesis that this loss is caused by feeding specializations. Specifically, feeding specializations were proposed to trigger time-dependent process of taste receptor loss through deprivation of benefit of using the receptor's gustatory function. We propose that this process may be accelerated by abiotic environmental conditions or decelerated/stopped because of extragustatory functions of the receptor's protein(s). As test case we used evolution of the sweet (TAS1R2+TAS1R3) and umami (TAS1R1+TAS1R3) receptors in Carnivora (dogs, cats, and kin). We predicted these receptors' absence/presence using data on presence/absence of inactivating mutations in these receptors' genes and data from behavioral sweet/umami preference tests. We identified 20 evolutionary events of sweet (11) or umami (9) receptor loss. These events affected species with feeding specializations predicted to favor sweet/umami receptor loss (27 and 22 species, respectively). All species with feeding habits predicted to favor sweet/umami receptor retention (11 and 24, respectively) were found to retain that receptor. Six species retained the sweet (5) or umami (1) receptor despite feeding specialization predicted to favor loss of that receptor, which can be explained by the time dependence of sweet/umami receptor loss process and the possible decelerating effect of TAS1R extragustatory functions so that the sweet/umami receptor process is ongoing in these species. Our findings support the idea that feeding specialization leads to taste receptor loss and is the main if not only triggering factor for evolutionary loss of taste receptors., (© The Author(s) 2022. Published by Oxford University Press.)

Gymnema sylvestre (GS) is a traditional medicinal plant known for its hypoglycemic and hypolipidemic effects. Gurmarin (hereafter Gur-1) is the only known active peptide in GS. Gur-1 has a suppressive sweet taste effect in rodents but no or only a very weak effect in humans. Here, 8 gurmarin-like peptides (Gur-2 to Gur-9) and their isoforms are reported in the GS transcriptome. The molecular mechanism of sweet taste suppression by Gur-1 is still largely unknown. Therefore, the complete architecture of human and mouse sweet taste receptors T1R2/T1R3 and their interaction with Gur-1 to Gur-9 were predicted by AlphaFold-Multimer (AF-M) and validated. Only Gur-1 and Gur-2 interact with the T1R2/T1R3 receptor. Indeed, Gur-1 and Gur-2 bind to the region of the cysteine-rich domain (CRD) and the transmembrane domain (TMD) of the mouse T1R2 subunit. In contrast, only Gur-2 binds to the TMD of the human T1R2 subunit. This result suggests that Gur-2 may have a suppressive sweet taste effect in humans. Furthermore, AF-M predicted that Gα-gustducin, a protein involved in sweet taste transduction, interacts with the intracellular domain of the T1R2 subunit. These results highlight an unexpected diversity of gurmarin-like peptides in GS and provide the complete predicted architecture of the human and mouse sweet taste receptor with the putative binding sites of Gur-1, Gur-2, and Gα-gustducin. In addition, gurmarin-like peptides may serve as promising drug scaffolds for the development of antidiabetic molecules., (© The Author(s) 2024. Published by Oxford University Press.)

Recent studies indicate that humans can taste starch hydrolysis products (i.e. maltooligosaccharides; MOS). However, the structural specificity of oligosaccharides that elicit such perception is not known. This study investigated taste perception of pullulan-derived oligosaccharides (PDOS) that are structurally similar to MOS, but differ in that every third glycosidic linkage in PDOS is α-1,6, rather than α-1,4. Three food-grade PDOS stimuli were produced by limited-enzyme hydrolysis of pullulan. The resulting products were stimuli with degree of polymerization (DP) of 3, 6, and 9. Subjects discriminated all 3 stimuli from blanks at a significant level (P < 0.00001) in the absence of lactisole, a sweet taste inhibitor. In the presence of lactisole, the subjects could not detect DP 3 at a significant level (P > 0.05), but were able to detect DP 6 and 9 (P < 0.005), although the degree of detectability dropped significantly (P < 0.05). In a follow-up qualitative study, subjects made the target stimuli and glucose into 2 groups (glucose/DP 3 vs. DP 6/DP 9) and characterized both groups as mostly "sweet" with having different sweetness intensity. With lactisole, they described glucose and DP 3 as "taste like blank" (lactisole water) and found it challenging to describe DP 6 and 9 stimuli due to their subtle nature. These results suggest that taste perception of PDOS primarily depends on the sweet taste receptor, although they may elicit other sensory attributes; this is strikingly different from the reported taste of MOS. The potential impact of structural configuration on taste perception is further discussed., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Deuterium oxide (D2O) is water in which the heavier and rare isotope deuterium replaces both hydrogens. We have previously shown that D2O has a distinctly sweet taste, mediated by the T1R2/T1R3 sweet taste receptor. Here, we explore the effect of heavy water on T1R2 and T1R3 subunits. We show that D2O activates T1R3-transfected HEK293T cells similarly to T1R2/T1R3-transfected cells. The response to glucose dissolved in D2O is higher than in water. Mutations of phenylalanine at position 7305.40 in the transmembrane domain of T1R3 to alanine, leucine, or tyrosine impair or diminish activation by D2O, suggesting a critical role for T1R3 TMD domain in relaying the heavy water signal., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Lopinavir and ritonavir (LPV/r) are the primary anti-human immunodeficiency virus (HIV) drugs recommended by the World Health Organization for treating children aged 3 years and above who are infected with the HIV. These drugs are typically available in liquid formulations to aid in dosing for children who cannot swallow tablets. However, the strong bitter taste associated with these medications can be a significant obstacle to adherence, particularly in young children, and can jeopardize the effectiveness of the treatment. Studies have shown that poor palatability can affect the survival rate of HIV-infected children. Therefore, developing more child-friendly protease inhibitor formulations, particularly those with improved taste, is critical for children with HIV. The molecular mechanism by which lopinavir and ritonavir activate bitter taste receptors, TAS2Rs, is not yet clear. In this study, we utilized a calcium mobilization assay to characterize the activation of bitter taste receptors by lopinavir and ritonavir. We discovered that lopinavir activates TAS2R1 and TAS2R13, while ritonavir activates TAS2R1, TAS2R8, TAS2R13, and TAS2R14. The development of bitter taste blockers that target these receptors with a safe profile would be highly desirable in eliminating the unpleasant bitter taste of these anti-HIV drugs., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The domestic cat (Felis catus) is an obligate carnivore, and as such has a meat-based diet. Several studies on the taste perception of cats have been reported, indicating that their sense of taste has evolved based on their carnivorous diet. Here, we propose that umami (mediated by Tas1r1-Tas1r3) is the main appetitive taste modality for the domestic cat by characterizing the umami taste of a range of nucleotides, amino acids, and their mixtures for cats obtained using complementary methods. We show for the first time that cats express Tas1r1 in taste papillae. The cat umami receptor responds to a range of nucleotides as agonists, with the purine nucleotides having the highest activity. Their umami receptor does not respond to any amino acids alone; however, 11 l-amino acids with a range of chemical characteristics act as enhancers in combination with a nucleotide. l-Glutamic acid and l-Aspartic acid are not active as either agonists or enhancers of the cat umami receptor due to changes in key binding residues at positions 170 and 302. Overall, cats have an appetitive behavioral response for nucleotides, l-amino acids, and their mixtures. We postulate that the renowned palatability of tuna for cats may be due, at least in part, to its specific combination of high levels of inosine monophosphate and free l-Histidine that produces a strong synergistic umami taste enhancement. These results demonstrate the critical role that the umami receptor plays in enabling cats to detect key taste compounds present in meat., (© The Author(s) 2023. Published by Oxford University Press.)

Ultra-processed food consumption has increased worldwide, yet little is known about the potential links with taste preference and sensitivity. This exploratory study aimed to (i) compare sweet and salty taste detection thresholds and preferences following consumption of ultra-processed and unprocessed diets, (ii) investigate whether sweet and salty taste sensitivity and preference were associated with taste substrates (i.e. sodium and sugar) and ad libitum nutrient intake, and (iii) examine associations of taste detection thresholds and preferences with blood pressure (BP) and anthropometric measures following consumption of ultra-processed and unprocessed diets. In a randomized crossover study, participants (N = 20) received ultra-processed or unprocessed foods for 2 weeks, followed by the alternate diet. Baseline food intake data were collected prior to admission. Taste detection thresholds and preferences were measured at the end of each diet arm. Taste-substrate/nutrient intake, body mass index (BMI), and body weight (BW) were measured daily. No significant differences were observed in participant salt and sweet detection thresholds or preferences after 2 weeks on ultra-processed or unprocessed diets. There was no significant association between salt and sweet taste detection thresholds, preferences, and nutrient intakes on either diet arm. A positive correlation was observed between salt taste preference and systolic BP (r = 0.59; P = 0.01), BW (r = 0.47, P = 0.04), and BMI (r = 0.50; P = 0.03) following consumption of the ultra-processed diet. Thus, a 2-week consumption of an ultra-processed diet does not appear to acutely impact sweet or salty taste sensitivity or preference. Trial Registration: ClinicalTrials.gov Identifier NCT03407053., (Published by Oxford University Press on behalf of US Government 2023.)

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., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

We have previously shown that l-glucose, the non-caloric enantiomer of d-glucose, activates the human sweet taste receptor T1R2/T1R3 transiently expressed in HEK293T cells. Here, we show that d- and l-glucose can also activate T1R2 and T1R3 expressed without the counterpart monomer. Serine mutation to alanine in residue 147 in the binding site of T1R3 VFT domain, completely abolishes T1R3S147A activation by either l- or d-glucose, while T1R2/T1R3S147A responds in the same way as T1R2 expressed without its counterpart. We further show that the original T1R2 reference sequence (NM&#95;152232.1) is less sensitive by almost an order of magnitude than the reference sequence at the time this study was performed (NM&#95;152232.4). We find that out of the four differing positions, it is the R317G in the VFT domain of T1R2, that is responsible for this effect in vitro. It is significant for both practical assay sensitivity and because glycine is found in this position in ~20% of the world population. While the effects of the mutations and the partial transfections were similar for d and l enantiomers, their dose-response curves remained distinct, with l-glucose reaching an early plateau., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Taste dysfunction has been associated with aging and is therefore thought to be less common in children. However, children can face medical conditions influencing their taste function. Measuring and understanding taste dysfunction in children may foster the development of treatments/interventions mitigating the detrimental effects of taste dysfunction on children's appetite and quality of life. But measuring loss of taste function requires adequate tools. This review was conducted to 1) provide an overview of etiologies (i.e., disease and iatrogenic) associated with taste dysfunction in a pediatric population; 2) to investigate which tools (psychophysical tests and questionnaires) are available to assess taste function in children; and 3) to identify what tools can be and are actually used in clinical practice. It is concluded that only a minority of available tools to assess taste function in children are readily suitable for a pediatric clinical setting. Considering the profound impact of taste dysfunction in the pediatric setting, developing, and implementing a standard taste test that is sensitive, simple, and practical to use with children is pertinent., (© The Author(s) 2021. Published by Oxford University Press.)

Recent anecdotal and scientific reports have provided evidence of a link between COVID-19 and chemosensory impairments, such as anosmia. However, these reports have downplayed or failed to distinguish potential effects on taste, ignored chemesthesis, and generally lacked quantitative measurements. Here, we report the development, implementation, and initial results of a multilingual, international questionnaire to assess self-reported quantity and quality of perception in 3 distinct chemosensory modalities (smell, taste, and chemesthesis) before and during COVID-19. In the first 11 days after questionnaire launch, 4039 participants (2913 women, 1118 men, and 8 others, aged 19-79) reported a COVID-19 diagnosis either via laboratory tests or clinical assessment. Importantly, smell, taste, and chemesthetic function were each significantly reduced compared to their status before the disease. Difference scores (maximum possible change ±100) revealed a mean reduction of smell (-79.7 ± 28.7, mean ± standard deviation), taste (-69.0 ± 32.6), and chemesthetic (-37.3 ± 36.2) function during COVID-19. Qualitative changes in olfactory ability (parosmia and phantosmia) were relatively rare and correlated with smell loss. Importantly, perceived nasal obstruction did not account for smell loss. Furthermore, chemosensory impairments were similar between participants in the laboratory test and clinical assessment groups. These results show that COVID-19-associated chemosensory impairment is not limited to smell but also affects taste and chemesthesis. The multimodal impact of COVID-19 and the lack of perceived nasal obstruction suggest that severe acute respiratory syndrome coronavirus strain 2 (SARS-CoV-2) infection may disrupt sensory-neural mechanisms.

Taste and other neurosensory defects have been reported postoperatively in a number of patients who have undergone mandibular third molar extraction (TME). Although the taste deficits are generally believed to resolve within a year, the long-term effects of TME remain unknown. We retrospectively examined the whole-mouth taste function of 891 individuals who had received TMEs, on average, more than 2 decades earlier, and 364 individuals who had not undergone TME. All had been extensively tested for chemosensory function at the University of Pennsylvania Smell and Taste Center over the course of the last 20 years. The whole-mouth identification test incorporated 2 presentations each of 5 different concentrations of sucrose, sodium chloride, citric acid, and caffeine. Analyses of covariance (age = covariate) found those with histories of TME to exhibit better overall test scores for all 4 taste qualities than nonoperated controls. Such scores were not associated with the time since the TME. In both groups, women outperformed men and function declined with age. The basis of this phenomenon, which requires confirmation from prospective studies, is unknown, but could reflect sensitization of CN VII nerve afferents or the partial release of the tonic inhibition that CN VII exerts on CN IX via central nervous system processes., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Outbred rats differ in their preference for the artificial sweetener sucralose. Psychophysical assessments have shown that the taste of sucralose is differentially generalized to either sucrose or a sucrose-quinine (QHCl) mixture in sucralose preferers (SP) and sucralose avoiders (SA), respectively. It remains to be determined if these differences in the psychophysical assessment of the taste of sucralose are due to an insensitivity to any bitter-like taste component of sucralose in SP or reduced sensitivity to a sweet-like component in SA that may mask any putative aversive side-taste in SP. Here, we exploited the proposed chemotopic organization of the rostral nucleus of the solitary tract (rNTS) to further parse out the root differences in the perception of the salient taste qualities of sucralose using Fos-like immunoreactivity (FLI) to approximate neural activation following intraoral delivery of sucrose, QHCl, and sucralose solutions in previously categorized SA and SP. First, we confirmed previous reports that the medial third of the NTS is primarily responsive to intraoral infusions of the bitter taste stimulus QHCl while sucrose produces a more diffuse pattern of FLI. Upon comparing the FLI generated by intraoral sucralose, we found that the pattern in SA was indistinguishable from that of QHCl while SP displayed a pattern of FLI more representative of a sucrose-QHCl mixture. We conclude that SA, relative to SP, may be less sensitive to the sucrose-like properties of sucralose and that an enhanced sensitivity to these sucrose-like qualities may mask a QHCl-like quality in SP., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Survivors of head and neck squamous cell cancers (HNSCC) frequently complain of taste dysfunction long after radiation therapy is completed, which contradicts findings from most sensory evaluation studies that predict dysfunction should resolve few months after treatment. Therefore, it remains unclear whether taste and smell function fully recovers in HNSCC survivors. We evaluated HNSCC survivors (n = 40; age 63 ± 12 years, mean ± standard deviation) who received radiation therapy between 6 months and 10 years before recruitment and compared their responses to those of a healthy control group (n = 20) equivalent in age, sex, race, smoking history, and body mass index. We assessed regional (tongue tip) and whole-mouth taste intensity perception using the general Labeled Magnitude Scale and smell function using the University of Pennsylvania Smell Identification Test (UPSIT). To determine possible differences between groups in retronasal smell perception, we used solutions of sucrose with strawberry extract, citric acid with lemon extract, sodium chloride in vegetable broth, and caffeine in coffee and asked participants to rate perceived smell and taste intensities with and without nose clips. We found groups had similar UPSIT and taste intensity scores when solutions were experienced in the whole mouth. However, HNSCC survivors were less likely to identify low concentrations of bitter, sweet, or salty stimuli in the tongue tip relative to healthy controls. Our findings suggest persistent and subtle localized damage to the chorda tympani or to the taste buds in the fungiform papillae of HNSCC survivors, which could explain their sensory complaints long after completion of radiotherapy., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Dopamine plays a key role in food rewards and sweet-taste stimulation. We examined the basis for behavioral responses to sweet taste in dopamine D3 receptor-deficient (D3-/-) mice by determining whether the absence of D3 receptors affects the sensitivity to dilute sucrose solutions. In experiment 1, we measured the intensity generalization threshold of conditioned taste aversion (CTA) to a 0.2 M sucrose solution. Results showed that the generalization thresholds were 0.025-0.05 M in D3-/- mice and 0.0025-0.005 M in wild-type (WT) mice. In experiment 2, we found that D3-/- and WT mice had similar capabilities to form and extinguish CTAs. Since the intensity generalization threshold is mainly due to a combination of sweet-taste sensitivity and the robust nature of CTA formation, the results showed that taste sensitivity to sucrose in D3-/- mice was lower than that in WT mice. In experiment 3, to test whether the peripheral sensory signaling may also be affected by the disruption of the dopamine D3 receptors, the mRNA expression levels of sweet-taste-related proteins in taste buds of D3-/- mice were determined. The T1R1 and BDNF mRNA expression levels in D3-/- mice were higher than the controls, whereas T1R2, T1R3, α-gustducin, and TRPM5 mRNA were similar. These findings suggest that disruption of dopamine D3 receptor-mediated signaling decreases the sweet-taste sensitivity and alters the mRNA expression levels of some taste-related molecules., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

In addition to the well-accepted taste receptors corresponding to the 6 basic taste qualities, sweet, salty, sour, bitter, umami, and fatty, another type of taste receptor, calcium-sensing receptor (CaSR), is located in taste bud cells. CaSR is called the kokumi receptor because its agonists induce koku (or kokumi), a Japanese word meaning the enhancement of flavor characteristics, such as thickness, mouthfulness, and continuity. Kokumi is an important factor in enhancing food palatability. γ-Glu-Val-Gly (EVG) is the most potent agonist of CaSR, which induces a strong kokumi flavor. However, no behavioral studies have been documented in animals using EVG. Here, we show that EVG at low concentrations that do not elicit a taste of its own enhances preferences for umami, fat, and sweet taste solutions in rats. An increased preference for inosine monophosphate (IMP) and Intralipos was the most dominant effect. NPS-2143, an antagonist of CaSR, abolished the additive effect of EVG on IMP and Intralipos solutions. These effects of EVG on taste stimuli are thought to occur in the oral cavity, because the effects of EVG were confirmed in a brief exposure test. The additive effects on IMP and Intralipos remained after the transection of the chorda tympani, indicating that these effects also occur in the palate and/or posterior part of the tongue. Moreover, the additive effects of EVG were verified in electrophysiological taste nerve responses. These results may partially provide the underlying mechanisms for EVG to induce kokumi flavor in humans., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Taste perception, initiated by activation of taste receptors in taste bud cells, is crucial for regulating nutrient intake. Genetic polymorphisms in taste receptor genes cannot fully explain the wide individual variations of taste sensitivity. Alternative splicing (AS) is a ubiquitous posttranscriptional mode of gene regulation that enriches the functional diversity of proteins. Here, we report the identification of a novel splicing variant of sweet taste receptor gene Tas1r2 (Tas1r2&#95;∆e4) in mouse taste buds and the mechanism by which it diminishes sweet taste responses in vitro and in vivo. Skipping of Tas1r2 exon 4 in Tas1r2&#95;∆e4 led to loss of amino acids in the extracellular Venus flytrap domain, and the truncated isoform reduced the response of sweet taste receptors (STRs) to all sweet compounds tested by generating nonfunctional T1R2/T1R3 STR heterodimers. The splicing factor PTBP1 (polypyrimidine tract-binding protein 1) promoted Tas1r2&#95;∆e4 generation through binding to a polypyrimidine-rich splicing silencer in Tas1r2 exon 4, thus decreasing STR function and sweet taste perception in mice. Taken together, these data reveal the existence of a regulated AS event in Tas1r2 expression and its effect on sweet taste perception, providing a novel mechanism for modulating taste sensitivity at the posttranscriptional level., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

CD36 and GNAT3 mediate taste responses, with CD36 acting as a lipid detector and GNAT3 acting as the α subunit of gustducin, a G protein governing sweet, savory, and bitter transduction. Strikingly, the genes encoding CD36 and GNAT3 are genomically superimposed, with CD36 completely encompassing GNAT3. To characterize genetic variation across the CD36-GNAT3 region, its implications for phenotypic diversity, and its recent evolution, we analyzed from ~2,500 worldwide subjects sequenced by the 1000 Genomes Project (1000GP). CD36-GNAT3 harbored extensive diversity including 8,688 single-nucleotide polymorphisms (SNPs), 414 indels, and other complex variants. Sliding window analyses revealed that nucleotide diversity and population differentiation across CD36-GNAT3 were consistent with genome-wide trends in the 1000GP (π = 0.10%, P = 0.64; FST = 9.0%, P = 0.57). In addition, functional predictions using SIFT and PolyPhen-2 identified 60 variants likely to alter protein function, and they were in weak linkage disequilibrium (r2 < 0.17), suggesting their effects are largely independent. However, the frequencies of predicted functional variants were low (P¯ = 0.0013), indicating their contributions to phenotypic variance on population scales are limited. Tests using Tajima's D statistic revealed that pressures from natural selection have been relaxed across most of CD36-GNAT3 during its recent history (0.39 < P < 0.67). However, CD36 exons showed signs of local adaptation consistent with prior reports (P < 0.035). Thus, CD36 and GNAT3 harbor numerous variants predicted to affect taste sensitivity, but most are rare and phenotypic variance on a population level is likely mediated by a small number of sites., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

People often confuse smell loss with taste loss, so it is unclear how much gustatory function is reduced in patients self-reporting taste loss. Our pre-registered cross-sectional study design included an online survey in 12 languages with instructions for self-administering chemosensory tests with 10 household items. Between June 2020 and March 2021, 10,953 individuals participated. Of these, 5,225 self-reported a respiratory illness and were grouped based on their reported COVID test results: COVID-positive (COVID+, N = 3,356), COVID-negative (COVID−, N = 602), and COVID unknown for those waiting for a test result (COVID?, N = 1,267). The participants who reported no respiratory illness were grouped by symptoms: sudden smell/taste changes (STC, N = 4,445), other symptoms excluding smell or taste changes (OthS, N = 832), and no symptoms (NoS, N = 416). Taste, smell, and oral irritation intensities and self-assessed abilities were rated on visual analog scales. Compared to the NoS group, COVID+ was associated with a 21% reduction in taste (95% confidence interval (CI): 15–28%), 47% in smell (95% CI: 37–56%), and 17% in oral irritation (95% CI: 10–25%) intensity. There were medium to strong correlations between perceived intensities and self-reported abilities (r = 0.84 for smell, r = 0.68 for taste, and r = 0.37 for oral irritation). Our study demonstrates that COVID-19-positive individuals report taste dysfunction when self-tested with stimuli that have little to none olfactory components. Assessing the smell and taste intensity of household items is a promising, cost-effective screening tool that complements self-reports and may help to disentangle taste loss from smell loss. However, it does not replace standardized validated psychophysical tests. [ABSTRACT FROM AUTHOR]

The brain combines gustatory, olfactory, and somatosensory information to create our perception of flavor. Within the somatosensory modality, texture attributes such as viscosity appear to play an important role in flavor preference. However, research into the role of texture in flavor perception is relatively sparse, and the contribution of texture cues to hedonic evaluation of flavor remains largely unknown. Here, we used a rat model to investigate whether viscosity preferences can be manipulated through association with nutrient value, and how viscosity interacts with taste to inform preferences for taste + viscosity mixtures. To address these questions, we measured preferences for moderately viscous solutions prepared with xanthan gum using 2-bottle consumption tests. By experimentally exposing animals to viscous solutions with and without nutrient value, we demonstrate that viscosity preferences are susceptible to appetitive conditioning. By independently varying viscosity and taste content of solutions, we further show that taste and viscosity cues both contribute to preferences for taste + viscosity mixtures. How these 2 modalities are combined depended on relative palatability, with mixture preferences falling in between component preferences, suggesting that hedonic aspects of taste and texture inputs are centrally integrated. Together, these findings provide new insight into how texture aspects of flavor inform hedonic perception and impact food choice behavior., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Taste buds are receptor organs for gustation. Two types of taste receptor cells have been identified in taste buds: Type II and Type III cells. Type III cells connect with afferent fibers through conventional chemical synapses. In the present study, we used immunocytochemistry to examine the distribution pattern of Bassoon, a scaffolding protein of the cytomatrix at the active zones of conventional synapses in mouse taste buds. Bassoon was predominantly detected as small puncta in Type III cells. Bassoon-immunoreactive puncta were observed in proximity to or partially overlapping with intragemmal nerve fibers. The distribution pattern of Bassoon in taste buds was similar among circumvallate, fungiform, and foliate taste buds. Immunoelectron microscopy showed Bassoon at the active zones of the conventional synapses of Type III cells in circumvallate taste buds. The present results demonstrate that Bassoon is a marker for synapses between Type III cells and afferent fibers in mouse taste buds., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Electrogustometry (EGM) is a practical way to test taste. It is typically performed using unipolar electrodes, with the anode on the tongue and the cathode on the hand, forearm, or neck. This results in electric current passing through nontaste tissues and adds a level of impracticality to its clinical application. We compared, using a repeated measures counterbalanced design, anodal thresholds from a unipolar electrode to those of a unique bipolar electrode in which the anode and cathode are contiguously located. Both sides of the anterior tongue were assessed in 70 subjects, as were the effects of age and sex. Nonparametric analyses were performed. The median threshold of the bipolar electrode's central disk (2.49 µA) did not differ from that of the unipolar electrode (2.96 µA) (P = 0.84). On average, older persons exhibited higher thresholds. No significant sex or tongue side effects were evident. Interestingly, when the annular (donut-shaped) bipolar electrode served as the anode, the threshold was higher than that of the other electrodes (5.19 µA; Ps < 0.001). This conceivably reflected lessened summation of activity among adjacent afferents and partial sampling of tongue regions with fewer taste buds. Correlations among all EGM thresholds were nominally higher for women than for men, ranging from 0.83 to 0.85 for women and 0.54 to 0.67 for men; all Ps < 0.001. This study validates the use of a bipolar electrode for assessing taste function, averting movement of current through nontaste-related tissues and making such testing safer and more practical., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Deuterium oxide (D2O) is water in which the heavier and rare isotope deuterium replaces both hydrogens. We have previously shown that D2O has a distinctly sweet taste, mediated by the T1R2/T1R3 sweet taste receptor. Here, we explore the effect of heavy water on T1R2 and T1R3 subunits. We show that D2O activates T1R3-transfected HEK293T cells similarly to T1R2/T1R3-transfected cells. The response to glucose dissolved in D2O is higher than in water. Mutations of phenylalanine at position 7305.40 in the transmembrane domain of T1R3 to alanine, leucine, or tyrosine impair or diminish activation by D2O, suggesting a critical role for T1R3 TMD domain in relaying the heavy water signal. [ABSTRACT FROM AUTHOR]

Chemosensory scientists have been skeptical that reports of COVID-19 taste loss are genuine, in part because before COVID-19 taste loss was rare and often confused with smell loss. Therefore, to establish the predicted prevalence rate of taste loss in COVID-19 patients, we conducted a systematic review and meta-analysis of 376 papers published in 2020-2021, with 235 meeting all inclusion criteria. Drawing on previous studies and guided by early meta-analyses, we explored how methodological differences (direct vs. self-report measures) may affect these estimates. We hypothesized that direct measures of taste are at least as sensitive as those obtained by self-report and that the preponderance of evidence confirms taste loss is a symptom of COVID-19. The meta-analysis showed that, among 138,015 COVID-19-positive patients, 36.62% reported taste dysfunction (95% confidence interval: 33.02%-40.39%), and the prevalence estimates were slightly but not significantly higher from studies using direct (n = 15) versus self-report (n = 220) methodologies (Q = 1.73, df = 1, P = 0.1889). Generally, males reported lower rates of taste loss than did females, and taste loss was highest among middle-aged adults. Thus, taste loss is likely a bona fide symptom of COVID-19, meriting further research into the most appropriate direct methods to measure it and its underlying mechanisms., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The lingual surface potential (LSP), which hyperpolarizes in response to salt and bitter stimuli, is thought to be a bioelectrical signal associated with taste transduction in humans. In contrast, a recent study reported sweet and sour stimuli to evoke a depolarization of the LSP. We questioned the origin of such a depolarization because liquid junction potentials (JPs), which arise at the interfaces of recording electrode and taste solutions, are neglected in the report. We recorded the LSPs to sucrose and NaCl solutions on the human tongue using an Ag/AgCl electrode. To estimate JPs generated by each taste solution, we made an agar model to simulate the human tongue. The lingual surface was rinsed with a 10 mM NaCl solution that mimics the sodium content of the lingual fluid. In the human tongue, sucrose dissolved in distilled water evoked a depolarizing LSP that could be attributed to JPs, resulting from the change in electrolyte concentration of the taste solution. Sucrose dissolved in 10 mM NaCl solution evoked a hyperpolarizing LSP which became more negative in a concentration-dependent manner (300-1500 mM). Lactisole (3.75 mM), an inhibitor of sweet taste, significantly reduced the LSPs and decreased perceived intensity of sweetness by human subjects. The negative JPs generated by 100 mM NaCl in the agar model were not different from the LSPs to 100 mM NaCl. When the electrolyte environment on the lingual surface is controlled for JPs, the bioelectrical signal associated with sweet taste transduction is a hyperpolarizing potential., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

In taste buds, Type I cells represent the majority of cells (50-60%) and primarily have a glial-like function in taste buds. However, recent studies suggest that they have additional sensory and signaling functions including amiloride-sensitive salt transduction, oxytocin modulation of taste, and substance P mediated GABA release. Nonetheless, the overall function of Type I cells in transduction and signaling remains unclear, primarily because of the lack of a reliable reporter for this cell type. GAD65 expression is specific to Type I taste cells and GAD65 has been used as a Cre driver to study Type I cells in salt taste transduction. To test the specificity of transgene-driven expression, we crossed GAD65Cre mice with floxed tdTomato and Channelrhodopsin (ChR2) lines and examined the progeny with immunochemistry, chorda tympani recording, and calcium imaging. We report that while many tdTomato+ taste cells express NTPDase2, a specific marker of Type I cells, we see some expression of tdTomato in both Gustducin and SNAP25-positive taste cells. We also see ChR2 in cells just outside the fungiform taste buds. Chorda tympani recordings in the GAD65Cre/ChR2 mice show large responses to blue light. Furthermore, several isolated tdTomato-positive taste cells responded to KCl depolarization with increases in intracellular calcium, indicating the presence of voltage-gated calcium channels. Taken together, these data suggest that GAD65Cre mice drive expression in multiple taste cell types and thus cannot be considered a reliable reporter of Type I cell function., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

A mouse single taste bud contains 10-100 taste bud cells (TBCs) in which the elongated TBCs are classified into 3 cell types (types I-III) equipped with different taste receptors. Accordingly, differences in the cell numbers and ratios of respective cell types per taste bud may affect taste-nerve responsiveness. Here, we examined the numbers of each immunoreactive cell for the type II (sweet, bitter, or umami receptor cells) and type III (sour and/or salt receptor cells) markers per taste bud in the circumvallate and foliate papillae and compared these numerical features of TBCs per taste bud to those in fungiform papilla and soft palate, which we previously reported. In circumvallate and foliate taste buds, the numbers of TBCs and immunoreactive cells per taste bud increased as a linear function of the maximal cross-sectional taste bud area. Type II cells made up approximately 25% of TBCs irrespective of the regions from which the TBCs arose. In contrast, type III cells in circumvallate and foliate taste buds made up approximately 11% of TBCs, which represented almost 2 times higher than what was observed in the fungiform and soft palate taste buds. The densities (number of immunoreactive cells per taste bud divided by the maximal cross-sectional area of the taste bud) of types II and III cells per taste bud are significantly higher in the circumvallate papillae than in the other regions. The effects of these region-dependent differences on the taste response of the taste bud are discussed., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Recent studies have shown the efficacy of a home test for the self-evaluation of olfactory and gustatory functions in quarantined coronavirus disease-2019 (COVID-19) patients. However, testing was often limited to COVID-19 participants, and the accuracy of home test kits was rarely compared to standardized testing. This study aims at providing proof of concept for the validation of the new Chemosensory Perception Test (CPT) developed to remotely assess orthonasal olfactory, retronasal olfactory, and gustatory functions in various populations using common North American household items. In the 2 experiments, a total of 121 participants irrespective of having olfactory and/or gustatory complaints from various causes (COVID-19, sinunasal, post-viral, idiopathic) were tested first, with one or many of the following tests: (i) a brief chemosensory questionnaire, (ii) an olfactory test-Sniffin' Sticks Test (SST) or University of Pennsylvania Smell Identification Test (UPSIT), and/or (iii) a gustatory test-Brief Waterless Empirical Taste Test (B-WETT). We then applied the CPT which yielded 3 different subscores, namely orthonasal, retronasal, and gustatory CPT scores. The orthonasal CPT score was significantly correlated with SST (ρ = 0.837, P < 0.001) and UPSIT (ρ = 0.364, P < 0.001) scores, and exhibited an excellent accuracy to identify olfactory dysfunction (OD) as compared to SST (area under the curve [AUC]: 0.923 [95% confidence interval {CI}, 0.822-1.000], P < 0.001). The retronasal CPT score but not the gustatory CPT score allowed to distinguish between participants with or without subjective gustatory complaint (AUC: 0.818 [95% CI, 0.726-0.909], P < 0.001). The CPT has the ability to identify OD and to quantify subjective gustatory complaints., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

A relationship between bitter and fat taste sensitivity, CD36 rs1761667 and TAS2R38 has been demonstrated. However, research is scarce and does not take diet into account. This study aimed to explore associations between genetics, fat and bitter taste sensitivity and dietary fat intake in healthy UK adults. A cross-sectional study was carried out on 88 Caucasian participants (49 females and 39 males aged 35 ± 1 years; body mass index 24.9 ± 0.5 kg/m2). Bitter taste sensitivity was assessed using phenylthiocarbamide (PTC) impregnated strips and the general Labeled Magnitude Scale. Fat taste sensitivity was assessed by the Ascending Forced Choice Triangle Procedure and dietary intake with a semi-quantitative food frequency questionnaire. Genotyping for rs713598, rs1726866, rs10246939, and rs1761667 was performed. Participants with TAS2R38 PAV/PAV diplotype perceived PTC strips as more bitter than groups carrying AVI haplotypes (AVI/AVI, P = 1 × 10-6; AVI/AAV, P = 0.029). CD36 rs1761667 was associated with fat taste sensitivity (P = 0.008). A negative correlation between bitter taste sensitivity and saturated fat intake was observed (rs = -0.256, P = 0.016). When combining the CD36 genotypes and TAS2R38 diplotypes into one variable, participants carrying both TAS2R38 AVI haplotype and CD36 A allele had a higher intake of saturated fat compared to carriers of CD36 GG genotype or TAS2R38 PAV/PAV and PAV/AAV diplotypes (13.8 ± 0.3 vs. 12.6 ± 0.5%TEI, P = 0.047) warranting further exploration in a larger cohort., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Bitter taste perception is critical to prevent animals from ingesting potentially harmful substances. The aim of this study was to characterize the evolution of T2R4 and test the hypothesis that different regions of the T2R gene are subject to disparate selective pressures, with extracellular regions (ECs) being erratic while transmembrane (TMs) and intracellular regions (ICs) being constrained. Thus, we examined the selective pressures acting on T2R4 and its different regions in 37 primates, and discovered that T2R4 and ECs were subject to neutral evolution and purifying selection, respectively, whereas both TMs and ICs showed purifying selection, as suggested by the hypothesis. We attribute this result to the relatively conservative property of T2R4 gene and the limited number of bitter tastants that T2R4 can respond to. Furthermore, we found that positive selection had acted on the first loop of extracellular regions (EL1). In contrast, the second loop (EL2) and transmembrane region-3, -6, -7 (TM367) were subject to purifying selection, and the third loop (EL3) was subject to neutral evolution. This discovery is probably because EL2, EL3, and TMs play a crucial role in the ligand-binding process, and EL1 is involved in the tastant recognition process. We further tested whether the ω of T2R4 differs among species with different diets and found that a specialized diet affected the evolution of T2R4. Feeding habits, fewer T2Rs, and a dietary shift may account for the results. This study can help to uncover the evolution of T2Rs during the primate evolutionary course., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Taste buds in the oral cavity have a complex immune system regulating normal functions and inflammatory reactions. Cyclophosphamide (CYP), a chemotherapy drug, has wide-ranging disruptive effects on the taste system including loss of taste function, taste sensory cells, and capacity for taste cell renewal. In bladder epithelium, CYP also induces inflammation. To determine if CYP induces inflammation in taste buds, we used immunohistochemistry to examine tumor necrosis factor alpha (TNF-α) (a proinflammatory cytokine) expression over a 72-hour period. Expression of TNF-α increased in a subset of PLCβ2 labeled (Type II) cells, but not SNAP-25 labeled (Type III) cells, between 8 and 24 h postinjection and declined slowly thereafter. This inflammatory response may play an important role in the disruptive effects of CYP on the taste system. Further, pretreatment with amifostine, a sulfhydryl drug known to protect normal tissues during chemo- or radiation therapy, reduced the amount of CYP-induced TNF-α expression in taste buds, suggesting this drug is capable of protecting normal cells of the taste system from adverse effects of CYP. Amifostine, used as a pretreatment to CYP and possibly other chemotherapy drugs, may offer clinical support for preventing negative side effects of chemotherapy on the taste system., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Bitter taste receptor genes (TAS2Rs) harbor extensive diversity, which is broadly distributed across human populations and strongly associated with taste response phenotypes. The majority of TAS2R variation is composed of single-nucleotide polymorphisms. However, 2 closely positioned loci at 12p13, TAS2R43 and -45, harbor high-frequency deletion (Δ) alleles in which genomic segments are absent, resulting in copy number variation (CNV). To resolve their chromosomal structure and organization, we generated maps using long-range contig alignments and local sequencing across the TAS2R43-45 region. These revealed that the deletion alleles (43Δ and 45Δ) are 37.8 and 32.2kb in length, respectively and span the complete coding region of each gene (~1kb) along with extensive up- and downstream flanking sequence, producing separate CNVs at the 2 loci. Comparisons with a chimpanzee genome, which contained intact homologs of TAS2R43, -45, and nearby TAS2Rs, indicated that the deletions evolved recently, through unequal recombination in a cluster of closely related loci. Population genetic analyses in 946 subjects from 52 worldwide populations revealed that copy number ranged from 0 to 2 at both TAS2R43 and TAS2R45, with 43Δ and 45Δ occurring at high global frequencies (0.33 and 0.18). Estimated recombination rates between the loci were low (ρ = 2.7×10(-4); r = 6.6×10(-9)) and linkage disequilibrium was high (D' = 1.0), consistent with their adjacent genomic positioning and recent origin. Geographic variation pointed to an African origin for the deletions. However, no signatures of natural selection were found in population structure or integrated haplotype scores spanning the region, suggesting that patterns of diversity at TAS2R43 and -45 are primarily due to genetic drift.

Oligosaccharides, a subclass of complex carbohydrates, occur both naturally in foods and as a result of oral starch digestion. We have previously shown that humans can taste maltooligosaccharides (MOS) and that their detection is independent of the canonical sweet taste receptor. While MOSs most commonly occur in a linear form, they can also exist in cyclic structures, referred to as cyclodextrins (CD). The aim of this study was to investigate how the structure of the MOS backbone (i.e. cyclic form) and the size (i.e. degree of polymerization; DP) affect their taste perception. We tested taste detection of cyclodextrins with DP of 6, 7, and 8 (i.e. α-, β-, and γ-CD, respectively) in the presence and absence of lactisole, a sweet receptor antagonist. We found that subjects could detect the taste of cyclodextrins in aqueous solutions at a significant level (P < 0.05), but were not able to detect them in the presence of lactisole (P > 0.05). These findings suggest that the cyclodextrins, unlike their linear analogs, are ligands of the human sweet taste receptor, hT1R2/hT1R3. Study findings are discussed in terms of how chemical structures may contribute to tastes of saccharides. [ABSTRACT FROM AUTHOR]

Among the 5 taste qualities, salt is the least understood. The receptors, their expression pattern in taste cells, and the transduction mechanisms for salt taste are still unclear. Previous studies have suggested that low concentrations of NaCl are detected by the amiloride-sensitive epithelial Na+ channel (ENaC), which in other systems requires assembly of 3 homologous subunits (α, β, and γ) to form a functional channel. However, a new study from Lossow and colleagues, published in this issue of Chemical Senses, challenges that hypothesis by examining expression levels of the 3 ENaC subunits in individual taste cells using gene-targeted mice in combination with immunohistochemistry and in situ hybridization. Results show a lack of colocalization of ENaC subunits in taste cells as well as expression of subunits in taste cells that show no amiloride sensitivity. These new results question the molecular identity of the amiloride-sensitive Na+ conductance in taste cells., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The chorda tympani (CT) nerve is exceptionally responsive to NaCl. Amiloride, an epithelial Na+ channel (ENaC) blocker, consistently and significantly decreases the NaCl responsiveness of the CT but not the glossopharyngeal (GL) nerve in the rat. Here, we examined whether amiloride would suppress the NaCl responsiveness of the CT when it cross-reinnervated the posterior tongue (PT). Whole-nerve electrophysiological recording was performed to investigate the response properties of the intact (CTsham), regenerated (CTr), and cross-regenerated (CT-PT) CT in male rats to NaCl mixed with and without amiloride and common taste stimuli. The intact (GLsham) and regenerated (GLr) GL were also examined. The CT responses of the CT-PT group did not differ from those of the GLr and GLsham groups, but did differ from those of the CTr and CTsham groups for some stimuli. Importantly, the responsiveness of the cross-regenerated CT to a series of NaCl concentrations was not suppressed by amiloride treatment, which significantly decreased the response to NaCl in the CTr and CTsham groups and had no effect in the GLr and GLsham groups. This suggests that the cross-regenerated CT adopts the taste response properties of the GL as opposed to those of the regenerated CT or intact CT. This work replicates the 5 decade-old findings of Oakley and importantly extends them by providing compelling evidence that the presence of functional ENaCs, essential for sodium taste recognition in regenerated taste receptor cells, depends on the reinnervated lingual region and not on the reinnervating gustatory nerve, at least in the rat., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Salt taste is one of the 5 basic taste qualities. Depending on the concentration, table salt is perceived either as appetitive or aversive, suggesting the contribution of several mechanisms to salt taste, distinguishable by their sensitivity to the epithelial sodium channel (ENaC) blocker amiloride. A taste-specific knockout of the α-subunit of the ENaC revealed the relevance of this polypeptide for low-salt transduction, whereas the response to other taste qualities remained normal. The fully functional ENaC is composed of α-, β-, and γ-subunits. In taste tissue, however, the precise constitution of the channel and the cell population responsible for detecting table salt remain uncertain. In order to examine the cells and subunits building the ENaC, we generated mice carrying modified alleles allowing the synthesis of green and red fluorescent proteins in cells expressing the α- and β-subunit, respectively. Fluorescence signals were detected in all types of taste papillae and in taste buds of the soft palate and naso-incisor duct. However, the lingual expression patterns of the reporters differed depending on tongue topography. Additionally, immunohistochemistry for the γ-subunit of the ENaC revealed a lack of overlap between all potential subunits. The data suggest that amiloride-sensitive recognition of table salt is unlikely to depend on the classical ENaCs formed by α-, β-, and γ-subunits and ask for a careful investigation of the channel composition., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The initial objective of this study was to determine if activation of the sweet taste receptor TAS1R2/TAS1R3 is necessary for perception of sweet thermal taste (swTT). Our approach was to inhibit the receptor with the inverse agonist lactisole using a temperature-controlled flow gustometer. Because all prior studies of thermal taste (TT) used metal thermodes to heat the tongue tip, we first investigated whether it could be generated in heated water. Experiment 1 showed that sweetness could be evoked when deionized water was heated from 20 to 35 °C, and testing with static temperatures between 20 and 35 °C demonstrated the importance of heating from a cool temperature. As in previous studies, thermal sweetness was reported by only a subset of participants, and replicate measurements found variability in reports of sweetness across trials and between sessions. Experiment 2 then showed that exposure to 8 mM lactisole blocked perception of swTT. Confirmation of the involvement of TAS1R2/TAS1R3 led to an investigation of possible sensory and cognitive interactions between thermal and chemical sweetness. Using sucrose as a sweet stimulus and quinine as a nonsweet control, we found that dynamic heating capable of producing thermal sweetness did not increase the sweetness of sucrose compared with static heating at 35 °C. However, swTT was disrupted if trials containing sucrose (but not quinine) were interspersed among heating-only trials. These findings provide new information relevant to understanding the perceptual processes and receptor mechanisms of swTT, as well as the heat sensitivity of sweet taste in general., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)