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Experimental or traumatic nerve injury causes the degeneration of associated taste buds. Unlike most sensory systems, the sectioned nerve and associated taste buds can then regenerate, restoring neural responses to tastants. It was previously unknown whether injury-induced immune factors mediate this process. The proinflammatory cytokines, interleukin (IL)-1a and IL-1b, and their requisite receptor are strongly expressed by anterior taste buds innervated by the chorda tympani nerve. We tested taste bud regeneration and functional recovery in mice lacking the IL-1 receptor. After axotomy, the chorda tympani nerve regenerated but was initially unresponsive to tastants in both WT and Il1r KO mice. In the absence of Il1r signaling, however, neural taste responses remained minimal even .8 weeks after injury in both male and female mice, whereas normal taste function recovered by 3 weeks in WT mice. Failed recovery was because of a 57.8% decrease in regenerated taste buds in Il1r KO compared with WT axotomized mice. Il1a gene expression was chronically dysregulated, and the subset of regenerated taste buds were reinnervated more slowly and never reached full volume as progenitor cell proliferation lagged in KO mice. Il1r signaling is thus required for complete taste bud regeneration and the recovery of normal taste transmission, likely by impairing taste progenitor cell proliferation. This is the first identification of a cytokine response that promotes taste recovery. The remarkable plasticity of the taste system makes it ideal for identifying injury-induced mechanisms mediating successful regeneration and recovery. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Taste substances are detected by taste receptor cells in the taste buds in the oral epithelium. Individual taste receptor cells contribute to evoking one of the five taste qualities: sweet, umami, bitter, sour, and salty (sodium). They are continuously replaced every few weeks by new ones generated from local epithelial stem cells. A POU transcription factor, Pou2f3 (also known as Skn-1a), regulates the generation and differentiation of sweet, umami, and bitter cells. However, the molecular mechanisms underlying terminal differentiation into these Pou2f3-dependent taste receptor cells remain unknown. To identify the candidate molecules that regulate the differentiation of these taste receptor cells, we searched for taste receptor type-specific transcription factors using RNA-sequence data of sweet and bitter cells. No transcription factor gene showing higher expression in sweet cells than in bitter cells was found. Eyes absent 1 (Eya1) was identified as the only transcription factor gene showing higher expression in bitter cells than in sweet cells. In situ hybridization revealed that Eya1 was predominantly expressed in bitter cells and also in the putative immature/differentiating taste bud cells in circumvallate and fungiform papillae and soft palate. Eya1 is a candidate molecule that regulates the generation and differentiation of bitter cells. [ABSTRACT FROM AUTHOR]

Background: Multicellular taste buds located within taste papillae on the tongue mediate taste sensation. In taste papillae, taste bud cells (TBCs), such as taste receptor cells and taste precursor cells, and the surrounding lingual epithelium including epithelial progenitors (also called taste stem/progenitor cells) are maintained by continuous cell turnover throughout life. However, it remains unknown how the cells constituting taste buds proliferate and differentiate to maintain taste bud tissue. Based on in situ hybridization (ISH) screening, we demonstrated that the oncofetal antigen 5T4 (also known as trophoblast glycoprotein: TPBG) gene is expressed in the adult mouse tongue.Results: In immunohistochemistry of coronal tongue sections, 5T4 protein was detected at a low level exclusively in the basal part of the lingual epithelium in developing and adult mice, and at a high level particularly in foliate papillae and circumvallate papillae (CVPs). Furthermore, immunohistochemistry of the basal part of CVPs indicated that the proliferation marker PCNA (proliferating cell nuclear antigen) co-localized with 5T4. 5T4 was strongly expressed in Krt5+ epithelial progenitors and Shh+ taste precursor cells, but weakly in mature taste receptor cells. The number of proliferating cells in the CVP was higher in 5T4-knockout mice than in wild-type (WT) mice, while neither cell differentiation nor the size of taste buds differed between these two groups of mice. Notably, X-ray irradiation enhanced cell proliferation more in 5T4-knockout mice than in WT mice.Conclusion: Our results suggest that 5T4, expressed in epithelial progenitors (taste stem/progenitor cells), and taste precursor cells, may influence the maintenance of taste papillae under both normal and injury conditions.

Background: Multicellular taste buds located within taste papillae on the tongue mediate taste sensation. In taste papillae, taste bud cells (TBCs), such as taste receptor cells and taste precursor cells, and the surrounding lingual epithelium including epithelial progenitors (also called taste stem/progenitor cells) are maintained by continuous cell turnover throughout life. However, it remains unknown how the cells constituting taste buds proliferate and differentiate to maintain taste bud tissue. Based on in situ hybridization (ISH) screening, we demonstrated that the oncofetal antigen 5T4 (also known as trophoblast glycoprotein: TPBG) gene is expressed in the adult mouse tongue. Results: In immunohistochemistry of coronal tongue sections, 5T4 protein was detected at a low level exclusively in the basal part of the lingual epithelium in developing and adult mice, and at a high level particularly in foliate papillae and circumvallate papillae (CVPs). Furthermore, immunohistochemistry of the basal part of CVPs indicated that the proliferation marker PCNA (proliferating cell nuclear antigen) co-localized with 5T4. 5T4 was strongly expressed in Krt5+ epithelial progenitors and Shh+ taste precursor cells, but weakly in mature taste receptor cells. The number of proliferating cells in the CVP was higher in 5T4- knockout mice than in wild-type (WT) mice, while neither cell differentiation nor the size of taste buds differed between these two groups of mice. Notably, X-ray irradiation enhanced cell proliferation more in 5T4 -knockout mice than in WT mice. Conclusion: Our results suggest that 5T4, expressed in epithelial progenitors (taste stem/progenitor cells), and taste precursor cells, may influence the maintenance of taste papillae under both normal and injury conditions. [ABSTRACT FROM AUTHOR]

Striking taste disturbances are reported in cancer patients treated with Hedgehog (HH)-pathway inhibitor drugs, including sonidegib (LDE225), which block the HH pathway effector Smoothened (SMO). We tested the potential for molecular, cellular, and functional recovery in mice from the severe disruption of taste-organ biology and taste sensation that follows HH/SMO signaling inhibition. Sonidegib treatment led to rapid loss of taste buds (TB) in both fungiform and circumvallate papillae, including disruption of TB progenitor-cell proliferation and differentiation. Effects were selective, sparing nontaste papillae. To confirm that taste-organ effects of sonidegib treatment result from HH/SMO signaling inhibition, we studied mice with conditional global or epithelium-specific Smo deletions and observed similar effects. During sonidegib treatment, chorda tympani nerve responses to lingual chemical stimulation were maintained at 10 d but were eliminated after 16 d, associated with nearly complete TB loss. Notably, responses to tactile or cold stimulus modalities were retained. Further, innervation, whichwasmaintained in the papilla core throughout treatment,was not sufficient to sustain TB during HH/SMO inhibition. Importantly, treatment cessation led to rapid and complete restoration of taste responses within 14 d associated with morphologic recovery in about 55% of TB. However, although taste nerve responses were sustained, TB were not restored in all fungiform papillae even with prolonged recovery for several months. This study establishes a physiologic, selective requirement for HH/SMO signaling in taste homeostasis that includes potential for sensory restoration and can explain the temporal recovery after taste dysgeusia in patients treated with HH/SMO inhibitors. [ABSTRACT FROM AUTHOR]

Rationale: Gustation is important to several biological functions in mammals. However, chemotherapy drugs often harm taste perception in cancer patients, while the underlying mechanism is still unclear for most drugs and there is no effective way to restore taste function. This study investigated the effects of cisplatin on the taste cell homeostasis and gustatory function. Methods: We used both mice and taste organoid models to study the effect of cisplatin on taste buds. Gustometer assay, gustatory nerve recording, RNA-Sequencing, quantitative PCR, and immunohistochemistry was performed to analyze the cisplatin-induced alteration in taste behavior and function, transcriptome, apoptosis, cell proliferation and taste cell generation. Results: Cisplatin inhibited proliferation and promoted apoptosis in the circumvallate papilla, leading to significant impairment in taste function and receptor cell generation. The transcriptional profile of genes associated with cell cycle, metabolic process and inflammatory response was significantly altered after cisplatin treatment. Cisplatin inhibited growth, promoted apoptosis, and deferred taste receptor cell differentiation in taste organoids. LY411575, a γ-secretase inhibitor, reduced the number of apoptotic cells and increased the number of proliferative cells and taste receptor cells, potentially suggesting as a taste tissue protective agent against chemotherapy. LY411575 treatment could offset the increased number of Pax1 + or Pycr1 + cells induced by cisplatin in the circumvallate papilla and taste organoids. Conclusion: This study highlights the inhibitory effects of cisplatin on taste cell homeostasis and function, identifies critical genes and biological processes regulated by chemotherapy, and proposes potential therapeutic targets and strategy for taste dysfunction in cancer patients., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Experimental or traumatic nerve injury causes the degeneration of associated taste buds. Unlike most sensory systems, the sectioned nerve and associated taste buds can then regenerate, restoring neural responses to tastants. It was previously unknown whether injury-induced immune factors mediate this process. The proinflammatory cytokines, interleukin (IL)-1α and IL-1β, and their requisite receptor are strongly expressed by anterior taste buds innervated by the chorda tympani nerve. We tested taste bud regeneration and functional recovery in mice lacking the IL-1 receptor. After axotomy, the chorda tympani nerve regenerated but was initially unresponsive to tastants in both WT and Il1r KO mice. In the absence of Il1r signaling, however, neural taste responses remained minimal even >8 weeks after injury in both male and female mice, whereas normal taste function recovered by 3 weeks in WT mice. Failed recovery was because of a 57.8% decrease in regenerated taste buds in Il1r KO compared with WT axotomized mice. Il1a gene expression was chronically dysregulated, and the subset of regenerated taste buds were reinnervated more slowly and never reached full volume as progenitor cell proliferation lagged in KO mice. Il1r signaling is thus required for complete taste bud regeneration and the recovery of normal taste transmission, likely by impairing taste progenitor cell proliferation. This is the first identification of a cytokine response that promotes taste recovery. The remarkable plasticity of the taste system makes it ideal for identifying injury-induced mechanisms mediating successful regeneration and recovery. SIGNIFICANCE STATEMENT Taste plays a critical role in nutrition and quality of life. The adult taste system is highly plastic and able to regenerate following the disappearance of most taste buds after experimental nerve injury. Several growth factors needed for taste bud regeneration have been identified, but we demonstrate the first cytokine pathway required for the recovery of taste function. In the absence of IL-1 cytokine signaling, taste bud regeneration is incomplete, preventing the transmission of taste activity to the brain. These results open a new direction in revealing injury-specific mechanisms that could be harnessed to promote the recovery of taste perception after trauma or disease., (Copyright © 2023 the authors.)

Taste buds are sensory organs in jawed vertebrates, composed of distinct cell types that detect and transduce specific taste qualities. Taste bud cells differentiate from oropharyngeal epithelial progenitors, which are localized mainly in proximity to the forming organs. Despite recent progress in elucidating the molecular interactions required for taste bud cell development and function, the cell behavior underlying the organ assembly is poorly defined. Here, we used time-lapse imaging to observe the formation of taste buds in live zebrafish larvae. We found that tg(fgf8a.dr17)-expressing cells form taste buds and get rearranged within the forming organs. In addition, differentiating cells move from the epithelium to the forming organs and can be displaced between developing organs. During organ formation, tg(fgf8a.dr17) and type II taste bud cells are displaced in random, directed or confined mode relative to the taste bud they join or by which they are maintained. Finally, ascl1a activity in the 5-HT/type III cell is required to direct and maintain tg(fgf8a.dr17)-expressing cells into the taste bud. We propose that diversity in displacement modes of differentiating cells acts as a key mechanism for the highly dynamic process of taste bud assembly. [ABSTRACT FROM AUTHOR]

Modulatory effects of pH and [Ca2+]i on taste receptor cell (TRC) epithelial sodium channel (ENaC) were investigated by monitoring chorda tympani (CT) responses to NaCl and KCl at various lingual voltages, before and after lingual application of ionomycin and with 0-10 mM CaCl2 in the stimulus and rinse solutions adjusted to pHo 2.0-9.7 . 0.1 and 0.5 M KCl responses varied continuously with voltage and were fitted to an apical ion channel kinetic model using the same parameters. ENaC-dependent NaCl CT response was fitted to the same channel model but with parameters characteristic of ENaC. A graded increase in TRC [Ca2+]i decreased the ENaC-dependent NaCl CT response, and inhibited and ultimately eliminated its pHi sensitivity. CT responses to KCl were pH- and [Ca2+]i-independent. Between ±60 mV applied lingual potential, the data were well described by a linear approximation to the nonlinear channel equation and yielded 2 parameters, the open-circuit response and the negative of the slope of the line in the CT response versus voltage plot, designated the response conductance. The ENaC-dependent NaCl CT response conductance was a linear function of the open-circuit response for all pHi-[Ca2+]i combinations examined. Analysis of these data shows that pHi and [Ca2+]i regulate TRC ENaC exclusively through modulation of the maximum CT response. [ABSTRACT FROM AUTHOR]

Highlights: [•] GR mRNA and protein were expressed in mouse taste buds. [•] CV taste tissue was enriched in GR mRNA compared to non-taste epithelium. [•] GR was coexpressed with the T1r3 sweet/umami taste receptor subunit in taste buds. [•] Restraint stress induced nuclear localization of GR in taste receptor cells. [ABSTRACT FROM AUTHOR]

Highlights: [•] We tested the effect of lipopolysaccharide (LPS) on peripheral taste responses. [•] Ingested LPS selectively and transiently inhibited neural responses to sucrose. [•] Neural effects were TLR4-dependent and accompanied by reduced T1R2+3 expression. [•] Limited exposure to a bacterial component alters taste input to the CNS. [ABSTRACT FROM AUTHOR]

Gypsy moth larvae are polyphagous feeders. The electrophysiological responses of the medial and lateral styloconic sensilla to four secondary compounds (e.g., alkaloids), two carbohydrates, and one inorganic salt were examined using an extracellular tip-recording method. In the medial sensillum, one taste receptor cell responded to the alkaloids, strychnine, caffeine, nicotine, and aristolochic acid (i.e., deterrent-sensitive cell), while another, responded to the sugar alcohol and inositol (inositol-sensitive cell). In both medial and lateral sensilla, two taste receptor cells in each sensillum responded minimally and sporadically to 30 mM potassium chloride (KCl) (i.e., KCl-sensitive cells); one cell produced much larger amplitude action potentials than the other. In the medial sensillum, only the large-amplitude KCl-sensitive cell exhibited an increased firing rate with increasing salt concentration. When binary mixture experiments were conducted, it was confirmed that the large-amplitude KCl-sensitive cell and the deterrent-sensitive cell in the medial sensillum were one in the same cell. Only a single cell in the lateral sensillum responded to the sugar, sucrose (sucrose-sensitive cell). The temporal dynamics of responses of the deterrent-sensitive, sucrose-sensitive, and inositol-sensitive cells were compared. Concentration-response data were obtained for the deterrent-sensitive cell to various alkaloids, as well as to KCl. [ABSTRACT FROM AUTHOR]

Gypsy moth larvae, Lymantria dispar (L.), are polyphagous feeders. The medial styloconic sensillum of this species bears a taste receptor cell that responds to alkaloids and another that responds to the sugar alcohol, inositol. The lateral styloconic sensillum bears a taste receptor cell that is sensitive to the sugar, sucrose. We tested the effect of two phagostimulants, namely sucrose and inositol, on the response of the deterrent-sensitive cell and found that both phagostimulants suppressed its response, equally, while their combination was significantly more effective. We also tested the effect of two alkaloids (i.e., strychnine and caffeine), which deter feeding in this species, on the response of the inositol- and sucrose-sensitive cells. Although both of these deterrents had no effect in suppressing the response of the sucrose-sensitive cell, they both had an effect in suppressing the inositol-sensitive cell. We also found that sucrose suppressed the response of the inositol-sensitive cell, whereas inositol had no significant effect on the response of the sucrose-sensitive cell. In this paper, we examined the effect of mixtures of these compounds to determine the nature of their interaction. In the context of host-plant interactions and, for example, host recognition, whereby host plant acceptability depends on the total sensory impression acquired from responses to multiple plant components rather than the presence or absence of single stimulant or deterrent compounds, this study could have a direct bearing in the development of natural compounds (i.e., alkaloids) for pest control and crop protection. It will also contribute to our understanding of the neural basis of the feeding behavior of this insect. [ABSTRACT FROM AUTHOR]

Abstract: The peripheral taste system remains plastic during adulthood. Sectioning the chorda tympani (CT) nerve, which sends sensory information from the anterior tongue to the central nervous system, causes degeneration of distal fibers and target taste buds. However, taste function is restored after about 40 days in young adult rodents. We tested whether aging impacts the reappearance of neural responses after unilateral CT nerve injury. Taste bud regeneration was minimal at day 50–65 after denervation, and most aged animals died before functional recovery could be assessed. A subset (n=3/5) of old rats exhibited normal CT responses at day 85 postsectioning, suggesting the potential for efficient recovery. The aged taste system is fairly resilient to sensory receptor loss and major functional changes in normal aging. However, injury to the taste system reveals a surprising vulnerability in old rodents. The gustatory system provides an excellent model to study mechanisms underlying delayed recovery from peripheral nerve injury. Strategies to accelerate recovery and restore normal function will be of interest, as the elderly population continues to grow. [Copyright &y& Elsevier]

Abstract: To visualize the neural pathways originating from bitter taste receptor cells (TRCs), we generated transgenic mice expressing the transneuronal tracer wheat germ agglutinin (WGA) under the control of the mouse T2R5 gene promoter/enhancer (t2r5-WGA mice). WGA mRNA was specifically expressed in bitter TRCs. The WGA protein was detected in bitter TRCs and nerve processes in taste buds, but not in sweet, umami, or sour TRCs. The WGA protein was transferred to a subset of sensory neurons in the geniculate and nodose/petrosal ganglia. These results suggest that bitter TRCs, which are devoid of synaptic structures, are innervated by gustatory neurons and that bitter sensory information is directly transmitted to specific gustatory neurons. The t2r5-WGA mice provide a useful tool for identifying gustatory relay neurons in the peripheral sensory ganglia responsible for aversive sensations. [ABSTRACT FROM AUTHOR]

Based on patch clamp data on the ionic currents of rat taste receptor cells, a mathematical model of mammalian taste receptor cells was constructed to simulate the action potentials of taste receptor cells and their corresponding ionic components, including voltage-gated Na+ currents and outward delayed rectifier K+ currents. Our simulations reproduced the action potentials of taste receptor cells in response to electrical stimuli or sour tastants. The kinetics of ion channels and their roles in action potentials of taste receptor cells were also analyzed. Our prototype model of single taste receptor cell and simulation results presented in this paper provide the basis for the further study of taste information processing in the gustatory system. [ABSTRACT FROM AUTHOR]

Neural pathways conveying taste information from the tongue to the brain underlie gustatory information coding and processing. To visualize the gustatory neural pathways, we established transgenic mouse lines in which a transneuronal tracer, wheat germ agglutinin (WGA), was faithfully and robustly expressed in sweet/umami taste receptor cells (TRCs) under the control of mouse T1R3 gene promoter/enhancer. WGA protein was transferred not laterally to the cells with synaptic structure, but directly to a subset of neurons in the geniculate and nodose/petrosal ganglia, and further conveyed to a subpopulation of neurons in the rostro-central region of the nucleus of the solitary tract. However, no WGA immunoreactivity was observed in more central gustatory relay nuclei even in the parabrachial nucleus. These results imply that sweet/umami information from TRCs can be directly transmitted to the gustatory neurons that innervate the sweet/umami TRCs, and this study uncovered a precise map of the sweet/umami information pathway from TRCs to the nucleus of solitary tract in the brain stem. [ABSTRACT FROM AUTHOR]

L-glutamate and 5′-ribonucleotides, such as GMP and IMP, elicit the “umami” taste, also known as the fifth taste. This review will highlight recent advancements in our understanding of umami taste receptors and their downstream signaling effectors in taste receptor cells. Several G protein-coupled receptors that bind umami stimuli have been identified in taste buds, including the heterodimer T1R1/T1R3, truncated and brain forms of mGluR4 and mGluR1, brain mGluR2, and brain mGluR3. Further, ionotropic glutamate receptors are expressed in taste cells and may play a role in glutamate transduction or signaling between taste cells and/or nerve fibers. Knockout of T1R1 or T1R3 reduces, but does not eliminate, responses to umami stimuli, suggesting that multiple receptors contribute to umami taste. The signaling effectors downstream of umami G protein-coupled receptors involve Gβγ activation of PLCβ2 to elicit Ca2+ release from intracellular stores and activation of a cation channel, TRPM5. In fungiform and palatal taste buds, T1R1/T1R3 is co-expressed with Gα gustducin and transducin, but the Gα proteins involved in circumvallate taste buds have not been identified. In most taste fields, however, cAMP antagonizes responses to umami stimuli, suggesting that the Gα subunit serves to modulate umami taste sensitivity. [ABSTRACT FROM AUTHOR]

Abstract: Taste receptor cell, the taste sensation organ with its intrinsic advantage of high sensitivity, specificity, fast response and powerful ability of information processing from taste system, can recognize taste substances. In order to investigate the electrophysiological signals of taste receptor cells and realize acidic sensation in a biomimetic manner, a cell-based biosensor platform of neuron–silicon interface was designed and characterized. Acid-sensing taste receptor cells were cultured on light-addressable potentiometric sensor (LAPS) to recognize sour stimuli as compared with non-acid solutions. A computational model of acid-sensing taste receptor cells was constructed to simulate the action potentials of taste receptor cells and to help decode the extracellular signals recorded by LAPS. The temporal firing and characteristic features from LAPS recordings upon acidic solutions demonstrate that this kind of hybrid biosensor based on taste receptor cells and LAPS can realize acidic sensation. This study also provides a prototype of a novel biosensor which deploys the sensory transduction and decoding mechanism from biology to realize chemosensing, potentially in a non-invasive and long-term manner. [Copyright &y& Elsevier]

Abstract: Previous studies have demonstrated that rodents'' chorda tympani (CT) nerve fibers responding to NaCl can be classified according to their sensitivities to the epithelial sodium channel (ENaC) blocker amiloride into two groups: amiloride-sensitive (AS) and -insensitive (AI). The AS fibers were shown to respond specifically to NaCl, whereas AI fibers broadly respond to various electrolytes, including NaCl. These data suggest that salt taste transduction in taste cells may be composed of at least two different systems; AS and AI ones. To further address this issue, we investigated the responses to NaCl, KCl and HCl and the amiloride sensitivity of mouse fungiform papilla taste bud cells which are innervated by the CT nerve. Comparable with the CT data, the results indicated that 56 NaCl-responsive cells tested were classified into two groups; 25 cells (∼44%) narrowly responded to NaCl and their NaCl response were inhibited by amiloride (AS cells), whereas the remaining 31 cells (∼56%) responded not only to NaCl, but to KCl and/or HCl and showed no amiloride inhibition of NaCl responses (AI cells). Amiloride applied to the basolateral side of taste cells had no effect on NaCl responses in the AS and AI cells. Single cell reverse transcription-polymerase chain reaction (RT-PCR) experiments indicated that ENaC subunit mRNA was expressed in a subset of AS cells. These findings suggest that the mouse fungiform taste bud is composed of AS and AI cells that can transmit taste information differently to their corresponding types of CT fibers, and apical ENaCs may be involved in the NaCl responses of AS cells. [Copyright &y& Elsevier]

Abstract: We established transgenic mouse lines expressing a transneuronal tracer, wheat germ agglutinin (WGA), under the control of mouse T1R3 gene promoter/enhancer. In the taste buds, WGA transgene was faithfully expressed in T1R3-positive sweet/umami taste receptor cells. WGA protein was transferred not laterally to the synapse-bearing, sour-responsive type III cells in the taste buds but directly to a subset of neurons in the geniculate and nodose/petrosal ganglia, and further conveyed to a rostro-central region of the nucleus of solitary tract. In addition, WGA was expressed in solitary chemoreceptor cells in the nasal epithelium and transferred along the trigeminal sensory pathway to the brainstem neurons. The solitary chemoreceptor cells endogenously expressed T1R3 together with bitter taste receptors T2Rs. This result shows an exceptional signature of receptor expression. Thus, the t1r3-WGA transgenic mice revealed the sweet/umami gustatory pathways from taste receptor cells and the trigeminal neural pathway from solitary chemoreceptor cells. [Copyright &y& Elsevier]

Abstract: Vertebrate taste receptor cells express signaling molecules such as taste receptors and effectors to convert taste stimuli to inner cellular signals. Phospholipase C-β2 (PLC-β2) is an effector enzyme that is necessary to transduce taste signals in the mouse. It was shown that a subset of the plc-β2 expressing cells also express taste receptor molecules, T1Rs or T2Rs, in mammals and fish. To label plc-β2 expressing cells in the model fish species, we constructed a transgene by linking the 5′-upstream region of the medaka plc-β2 gene to a green fluorescent protein (GFP) gene. The resulting transgenic medaka exhibited GFP signals in taste buds of the lips and the pharyngeal region. Detailed observation revealed that the GFP signals were in a subpopulation of taste bud cells, and co-localized with the transcript of endogenous plc-β2 gene. Zebrafish introduced with the same transgene showed GFP signals in a subpopulation of taste bud cells of the lips and the pharyngeal region as in the case of medaka. This is the first report of successful labeling of taste receptor cells in two model fish species under the control of the plc-β2 promoter. This promoter will be a useful genetic tool to study the vertebrate taste system in general. [Copyright &y& Elsevier]

The article discusses the study which investigates how intracellular Ca(2+) increases in the umami transduction pathway. The researchers have measured the changes in the intracellular Ca(2+) levels in response to umami stimuli monosodium glutamate, inosine 5'-monophosphate or both in mouse taste receptor cells (TRCs) by Ca(2+) imaging. Results indicate that umami-responsive TRCs have increased their intracellular Ca(2+) levels through two pathways.

We investigated the relationship between the membrane potential of frog taste cells in the fungiform papillae and the tonic discharge of parasympathetic efferent fibers in the glossopharyngeal (GP) nerve. When the parasympathetic preganglionic fibers in the GP nerve were kept intact, the mean membrane potential of Ringer-adapted taste cells was −40 mV but decreased to −31 mV after transecting the preganglionic fibers in the GP nerve and crushing the postganglionic fibers in the papillary nerve. The same result occurred after blocking the nicotinic acetylcholine receptors on parasympathetic ganglion cells in the tongue and blocking the substance P neurokinin-1 (NK-1) receptors in the gustatory efferent synapses. This indicates that the parasympathetic nerve (PSN) hyperpolarizes the membrane potential of frog taste cells by −9 mV. Repetitive stimulation of a transected GP nerve revealed that a −9-mV hyperpolarization of taste cells maintained under the intact GP nerve derives from an ∼10-Hz discharge of the PSN efferent fibers. The mean frequency of tonic discharges extracellularly recorded from PSN efferent fibers of the taste disks was 9.1 impulses/s. We conclude that the resting membrane potential of frog taste cells is continuously hyperpolarized by on average −9 mV by an ∼10-Hz tonic discharge from the parasympathetic preganglionic neurons in the medulla oblongata. [ABSTRACT FROM AUTHOR]

Taste reception is fundamental for proper selection of food and beverages. Chemicals detected as taste stimuli by vertebrates include a large variety of substances, ranging from inorganic ions (e.g., Na+, H+) to more complex molecules (e.g., sucrose, amino acids, alkaloids). Specialized epithelial cells, called taste receptor cells (TRCs), express specific membrane proteins that function as receptors for taste stimuli. Classical view of the early events in chemical detection was based on the assumption that taste substances bind to membrane receptors in TRCs without permeating the tissue. Although this model is still valid for some chemicals, such as sucrose, it does not hold for small ions, such as Na+, that actually diffuse inside the taste tissue through ion channels. Electrophysiological, pharmacological, biochemical, and molecular biological studies have provided evidence that indeed TRCs use ion channels to reveal the presence of certain substances in foodstuff. In this review, we focus on the functional and molecular properties of ion channels that serve as receptors in taste transduction. [Copyright &y& Elsevier]

Chili pepper is one of most widely used spices. The main active component of chili pepper is the capsaicin. The effects of capsaicin on sensory nerve endings are well known; however, little is known regarding the direct effect of capsaicin on taste receptor cells (TRCs). In this study, patch clamp methods were used to study the effects of capsaicin on the K+ currents in TRCs isolated from the rat circumvallate papilla. Fura-2 microspectrofluorimetry was also used to determine the effects of capsaicin on the intracellular Ca2+ concentration ([Ca2+]i). In the resting state, whole-cell experiments identified outward-rectifying K+ currents, which were inhibited by 5 mM tetraethylammonium (TEA+) chloride. Voltage-dependent K+ channels with a conductance of 55±4 pS (mean±S.E.M.; n=3), were observed in cell-attached patches. Capsaicin (500 nM) completely inhibited the outward-rectifying K+ current in the whole-cell recordings. In cell-attached patches 500 nM capsaicin significantly reduced the open probability (Po) of the K+ channels from 0.401±0.052 (n=3) in the resting state, to 0.018±0.002 (n=3, P<0.05 by unpaired t-test). In the fura-2-loaded TRCs, micromolar concentrations of capsaicin increased [Ca2+]i in a dose-dependent manner, e.g., 100 μM capsaicin consistently increased the 340:380 fluorescence ratio from 1.04±0.05 in the resting state to 1.40±0.05 (n=28). These results suggest that capsaicin can enhance or modify the gustatory sensation by inhibiting the K+ currents of the TRCs directly. [Copyright &y& Elsevier]

Differences in taste bud ultrastructure between active and low-temperature hibernation states were investigated in the Siberian ground squirrel, Citellus undulatus. Compared to active summer animals, taste bud volume and the morphology of the taste pore showed little change while an animal was hibernating. However, impressive differences were observed in nuclei and cytoplasmic organelles of all cells within taste buds. In low-temperature hibernation the nucleoli of elongated, non-dark cells had few, but large, fibrillar centres, a sign of inactivity. In the cytoplasm, the number of free polyribosomes (polysomes) was sharply decreased; ribosomes were seen mainly as (non-synthesizing) monosomes and more seldom as membraneassociated ribosomes. Profiles of endoplasmic reticulum (ER) were reduced, to the extent that only separate and rare cisternae of smooth and rough ER remained. The large vacuoles, which are typically found in many taste cells of active animals, were absent during hibernation, and the Golgi apparatus appeared to be disassembled into numerous vesicles. Of these, many had small diameters near 60 nm, while a few had larger diameters near 300 nm. Secretory organelles (dense granules in dark cells and dense-cored vesicles in type III cells) were rare during hibernation, the lateral plasma membrane was smooth, and signs of exocytosis were not found. These changes suggest reduced protein synthesis and reduced sensory function during hibernation. [ABSTRACT FROM AUTHOR]

Modulatory effects of pHi and [Ca(2+)]i on taste receptor cell (TRC) epithelial sodium channel (ENaC) were investigated by monitoring chorda tympani (CT) responses to NaCl and KCl at various lingual voltages, before and after lingual application of ionomycin and with 0-10mM CaCl2 in the stimulus and rinse solutions adjusted to pHo 2.0-9.7. 0.1 and 0.5M KCl responses varied continuously with voltage and were fitted to an apical ion channel kinetic model using the same parameters. ENaC-dependent NaCl CT response was fitted to the same channel model but with parameters characteristic of ENaC. A graded increase in TRC [Ca(2+)]i decreased the ENaC-dependent NaCl CT response, and inhibited and ultimately eliminated its pH sensitivity. CT responses to KCl were pHi- and [Ca(2+)]i-independent. Between ±60 mV applied lingual potential, the data were well described by a linear approximation to the nonlinear channel equation and yielded 2 parameters, the open-circuit response and the negative of the slope of the line in the CT response versus voltage plot, designated the response conductance. The ENaC-dependent NaCl CT response conductance was a linear function of the open-circuit response for all pHi-[Ca(2+)]i combinations examined. Analysis of these data shows that pHi and [Ca(2+)]i regulate TRC ENaC exclusively through modulation of the maximum CT response., (© The Author 2015. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)