The molecular and cellular basis of bitter taste in Drosophila

The extent of diversity among bitter-sensing neurons is a fundamental issue in the field of taste. Data are limited and conflicting as to whether bitter neurons are broadly tuned and uniform, resulting in indiscriminate avoidance of bitter stimuli, or diverse, allowing a more discerning evaluation of food sources. We provide a systematic analysis of how bitter taste is encoded by the major taste organ of the Drosophila head, the labellum. Each of 16 bitter compounds is tested physiologically against all 31 taste hairs, revealing responses that are diverse in magnitude and dynamics. Four functional classes of bitter neurons are defined. Four corresponding classes are defined through expression analysis of all 68 gustatory taste receptors. A receptor-to-neuron-to-tastant map is constructed. Misexpression of one receptor confers bitter responses as predicted by the map. These results reveal a degree of complexity that greatly expands the capacity of the system to encode bitter taste.     

Tasteless food reward

Food palatability acts on the dopaminergic reward system to override homeostatic control; however, whether postingestive calorie load in the absence of taste affects this system remains unclear. In this issue of Neuron, de Araujo et al. show that mice lacking functional "sweet" taste receptors (trpm5-/-) develop a preference for sucrose by activating the mesolimbic dopamine-accumbal pathway, solely based on calorie load.     

Taste receptor cell-based biosensor for taste specific recognition based on temporal firing

Taste receptor cells are the taste sensation elements expressing sour, salty, sweet, bitter and umami receptors, respectively. There are cell-to-cell communications between different types of cells. Nevertheless, the mechanism of taste sensation and taste information coded by taste receptor cell is not well understood at present and it is a long-standing issue. In order to explore taste sensation and analyze taste-firing responses from another point of view, we present a promising biomimetic taste receptor cell-based biosensor. The temporal firing responses to different tastants are recorded. Meanwhile, we investigate the firing rate and temporal firing of taste receptor cells. The experimental results are consistent with that from patch clamp and molecular biology experiment. Firing rate is dependent on the concentration of stimulus. PCA analysis (principal component analysis) of the temporal firing responses shows that the responses from different types of taste receptor cells can be distinguished. Furthermore, exogenous ATP is applied to mimic the effects of transmitter ATP (adenosine triphosphate) released from type II cells onto type III cells. Both enhanced and inhibitory effects on spontaneous firing are observed. This novel biomimetic hybrid biosensor provides a potential solution to investigate the taste sensation and coding mechanisms in a non-invasive way.     

Concentrations of NaCl and sucrose: equality in perceived taste intensity

Results from previous studies suggest that sucrose and NaClsolutions have an equal perceived taste intensity when the molarconcentration of sucrose is 1.5–1.75 times the molar concentrationof NaCl. However, according to other studies, sucrose and NaClsolutions taste equally strong when their molar concentrationsare about equal. This issue was further pursued using the methodof constant stimuli, where subjects matched the perceived tasteintensity of NaCl solutions to five sucrose references and viceversa. The results concur with previous findings that sucroseand NaCl solutions have equal perceived taste intensities whenthe molar concentration of sucrose is 1.5–1.75 times themolar concentration of NaCl.     

Experimentally cross-wired lingual taste nerves can restore normal unconditioned gaping behavior in response to quinine stimulation

Studies examining the effects of transection and regeneration of the glossopharyngeal (GL) and chorda tympani (CT) nerves on various taste-elicited behaviors in rats have demonstrated that the GL (but not the CT) nerve is essential for the maintenance of both an unconditioned protective reflex (gaping) and the neural activity observed in central gustatory structures in response to lingual application of a bitter substance. An unresolved issue, however, is whether recovery depends more on the taste nerve and the central circuits that it supplies and/or on the tongue receptor cell field being innervated. To address this question, we experimentally cross-wired these taste nerves, which, remarkably, can regenerate into parts of the tongue they normally do not innervate. We report that quinine-stimulated gaping behavior was fully restored, and neuronal activity, as assessed by Fos immunohistochemistry in the nucleus of the solitary tract and the parabrachial nucleus, was partially restored only if the posterior tongue (PT) taste receptor cell field was reinnervated; the particular taste nerve supplying the input was inconsequential to the recovery of function. Thus, PT taste receptor cells appear to play a privileged role in triggering unconditioned gaping to bitter tasting stimuli, regardless of which lingual gustatory nerve innervates them. Our findings demonstrate that even when a lingual gustatory nerve (the CT) forms connections with taste cells in a non-native receptor field (the PT), unconditioned taste rejection reflexes to quinine can be maintained. These findings underscore the extraordinary ability of the gustatory system to adapt to peripherally reorganized input for particular behaviors.     

Bitter Taste Receptors Influence Glucose Homeostasis

TAS1R- and TAS2R-type taste receptors are expressed in the gustatory system, where they detect sweet- and bitter-tasting stimuli, respectively. These receptors are also expressed in subsets of cells within the mammalian gastrointestinal tract, where they mediate nutrient assimilation and endocrine responses. For example, sweeteners stimulate taste receptors on the surface of gut enteroendocrine L cells to elicit an increase in intracellular Ca²⁺ and secretion of the incretin hormone glucagon-like peptide-1 (GLP-1), an important modulator of insulin biosynthesis and secretion. Because of the importance of taste receptors in the regulation of food intake and the alimentary responses to chemostimuli, we hypothesized that differences in taste receptor efficacy may impact glucose homeostasis. To address this issue, we initiated a candidate gene study within the Amish Family Diabetes Study and assessed the association of taste receptor variants with indicators of glucose dysregulation, including a diagnosis of type 2 diabetes mellitus and high levels of blood glucose and insulin during an oral glucose tolerance test. We report that a TAS2R haplotype is associated with altered glucose and insulin homeostasis. We also found that one SNP within this haplotype disrupts normal responses of a single receptor, TAS2R9, to its cognate ligands ofloxacin, procainamide and pirenzapine. Together, these findings suggest that a functionally compromised TAS2R receptor negatively impacts glucose homeostasis, providing an important link between alimentary chemosensation and metabolic disease.     

Decrease in rat taste receptor cell intracellular pH is the proximate stimulus in sour taste transduction

Taste receptor cells (TRCs)respond to acid stimulation, initiating perception of sour taste.Paradoxically, the pH of weak acidic stimuli correlates poorly with theperception of their sourness. A fundamental issue surrounding sourtaste reception is the identity of the sour stimulus. We tested thehypothesis that acids induce sour taste perception by penetratingplasma membranes as H⁺ ions or as undissociated moleculesand decreasing the intracellular pH (pH_i) of TRCs. Our datasuggest that taste nerve responses to weak acids (acetic acid andCO₂) are independent of stimulus pH but strongly correlatewith the intracellular acidification of polarized TRCs. Taste nerveresponses to CO₂ were voltage sensitive and were blockedwith MK-417, a specific blocker of carbonic anhydrase. Strong acids(HCl) decrease pH_i in a subset of TRCs that contain apathway for H⁺ entry. Both the apical membrane and theparacellular shunt pathway restrict H⁺ entry such that alarge decrease in apical pH is translated into a relatively smallchange in TRC pH_i within the physiological range. Weconclude that a decrease in TRC pH_i is the proximate stimulus in rat sour taste transduction.

     

CLASSIFICATION OF CHEESES ACCORDING TO THEIR CLOSENESS TO THE CHEDDAR CHEESE CONCEPT1

An important issue in consumer oriented studies is to measure how closely a specific product or perception matches the representation people have of it. We used a concept matching technique to assess the degree to which a variety of different cheeses matched subjects’ concepts of Cheddar cheese. Eighteen subjects made their judgments using their own past experiences with Cheddar cheeses. They made judgments in three separate conditions: only the odor, only the taste and texture and normal eating. This technique provided valid and reliable information on the extent to which the cheeses matched the subjects’ concept of Cheddar cheese. Agreement between classifications of cheeses based on taste and texture only and based on normal eating was high (R=0.90). Agreement between classifications based only on odor and those based on normal eating was weaker (R-0.59). Thus, the taste and texture of the cheeses were more useful than the odor for classifying cheeses as Cheddar.     

A taste of what to expect: top-down modulation of neural coding in rodent gustatory cortex

A central aspect of sensory perception is the anticipation of forthcoming stimuli, allowing for a faster and more accurate assessment of the surrounding environment. A new study by Samuelsen et?al. (2012) in this issue of Neuron highlights the neural mechanisms underlying the expectation of an imminent taste.     

Determination of the taste threshold of copper in water

Copper effects on human health represent a relevant issue in modern nutrition. One of the difficulties in assessing the early, acute effects of copper ingested via drinking water is that the taste of copper may influence the response and the capacity to taste copper in different waters is unknown. The purpose of the study was to determine the taste threshold of copper in different types of water, using soluble and insoluble salts (copper sulfate and copper chloride). Copper-containing solutions (range 1.0-8.0 mg/l Cu) were prepared in tap water, distilled deionized water and uncarbonated mineral water. Sixty-one healthy volunteers (17-50 years of age), with no previous training for sensory evaluation, participated in the study. A modified triangle test was used to define the taste threshold value. The threshold was defined as the lowest copper concentration detected by 50% of the subjects assessed. To evaluate the olfactory input in the threshold value obtained, 15 of 61 subjects underwent a second set of triangle tests with the nose open and clamped, using distilled water with copper sulfate at a concentration corresponding to the individual's threshold. The taste threshold in tap water was 2.6 mg/l Cu for both copper sulfate and copper chloride. The corresponding values for distilled deionized water were 2.4 and 2.5 mg/l Cu for copper sulfate and copper chloride, respectively. In uncarbonated mineral water the threshold values were slightly higher, 3.5 and 3.8 mg/l Cu for copper sulfate and for copper chloride, respectively, which are significantly higher than those observed in tap and distilled waters (P < 0.01, Kruskal-Wallis test). The taste threshold did not change significantly when the nose was clamped. In conclusion, the median values for copper taste threshold were low, ranging between 2.4 and 3.8 mg/l Cu, depending on the type of water.     

Expression of catfish amino acid taste receptors inXenopus oocytes

We demonstrate that poly (A⁺)RNA isolated from catfish barbels directs the expression of functional amino acid taste receptors in theXenopus oocyte. The activity of these receptors is monitored in ovo by the two electrode voltage clamp technique. Specific conductance changes recorded in response to amino acid stimulation are analogous to those recorded electrophysiologically from intact catfish barbels. These responses exhibit specificity, reproducibility, rapid onset and termination, and desensitization to repetitive stimulation. A functional assay system that encompasses the full complement of transduction events from the ligand-receptor interaction to subsequent conductance changes is necessary to identify molecular components responsible for these events. Our results demonstrate that theXenopus oocyte can be used to characterize and identify clones coding for amino acid taste receptors analogous to its use in studying receptor molecules for other neuroactive compounds.Special issue is dedicated to Dr. Sidney Udenfriend.     

Fataluku medicinal ethnobotany and the East Timorese military resistance

In recent years, diverse scholars have addressed the issue of the chemosensory perceptions associated with traditional medicines, nevertheless there is still a distinct lack of studies grounded in the social sciences and conducted from a cross-cultural, comparative perspective. In this urban ethnobotanical field study, 254 informants belonging to the Gujarati, Kashmiri and English ethnic groups and living in Western Yorkshire in Northern England were interviewed about the relationship between taste and medicinal perceptions of five herbal drugs, which were selected during a preliminary study. The herbal drugs included cinnamon (the dried bark of Cinnamomum verum, Lauraceae), mint (the leaves of Mentha spp., Lamiaceae), garlic (the bulbs of Allium sativum, Alliaceae), ginger (the rhizome of Zingiber officinale, Zingiberaceae), and cloves (the dried flower buds of Syzygium aromaticum, Myrtaceae). The main cross-cultural differences in taste perceptions regarded the perception the perception of the spicy taste of ginger, garlic, and cinnamon, of the bitter taste of ginger, the sweet taste of mint, and of the sour taste of garlic. The part of the study of how the five selected herbal drugs are perceived medicinally showed that TK (Traditional Knowledge) is widespread among Kashmiris, but not so prevalent among the Gujarati and especially the English samples. Among Kashmiris, ginger was frequently considered to be helpful for healing infections and muscular-skeletal and digestive disorders, mint was chosen for healing digestive and respiratory troubles, garlic for blood system disorders, and cinnamon was perceived to be efficacious for infectious diseases. Among the Gujarati and Kashmiri groups there was evidence of a strong link between the bitter and spicy tastes of ginger, garlic, cloves, and cinnamon and their perceived medicinal properties, whereas there was a far less obvious link between the sweet taste of mint and cinnamon and their perceived medicinal properties, although the link did exist among some members of the Gujarati group. Data presented in this study show how that links between taste perceptions and medicinal uses of herbal drugs may be understood as bio-cultural phenomena rooted in human physiology, but also constructed through individual experiences and culture, and that these links can therefore be quite different across diverse cultures.     

Electrophysiological heterogeneity in a functional subset of mouse taste cells during postnatal development

Taste cells in adult mammals are functionally heterogeneous as to the expression of ion channels. How these adult phenotypes are established during postnatal development, however, is not yet clear. We have addressed this issue by studying voltage-gated K(+) and Cl(-) currents (I(K) and I(Cl), respectively) in developing taste cells of the mouse vallate papilla. I(K) and I(Cl) underlie action potential waveform and firing properties, and play an important role in taste transduction. By using the patch clamp technique, we analyzed these currents in a specific group of cells, called Na/OUT cells and thought to be sensory. In adult mice, three different electrophysiological phenotypes of Na/OUT cells could be detected: cells with I(K) (K cells); cells with both I(K) and I(Cl) (K+Cl cells); and cells with I(Cl) (Cl cells). In contrast, at early developmental stages (2-4 postnatal days, PD) there were no Cl cells, which appeared at PD 8. Our findings indicate a mechanism that contributes to building-up the functional heterogeneity of mammalian taste cells during the postnatal development.     

Salt taste and salt sensitivity in black adolescents

Limited support for the postulated association between tasteand blood pressure responses to NaCl has prompted investigationsof selected subgroups of subjects more likely to display a relationship.The present study included 20 black adolescents who were diagnosedas salt sensitive (n = 10) or salt insensitive (n = 10) basedupon blood pressure responses to 14 days of dietary salt loading(10 g NaCl/day). Each was administered a battery of taste tests,including measures of detection and recognition threshold, suprathresholdintensity responses and preference tests. No significant groupdifference was observed on any taste measure. While explanationsfor the failure to note differences between these individualswith marked variabilty in systemic reactivity to NaCl are offered,the present findings question the continued study of this issue.     

On the Relationship between the Indirectly Measured Attitude Towards Beer and Beer Consumption: The Role of Attitude Accessibility

Although some studies have demonstrated that the indirectly measured attitude towards alcohol is related to alcohol use, this relationship has not always been confirmed. In the current study, we attempted to shed light on this issue by investigating whether the predictive validity of an indirect attitude measure is dependent upon attitude accessibility. In a sample of 88 students, the picture-picture naming task, an adaptation of the affective priming paradigm, was used to measure the automatically activated attitude towards beer. Attitude accessibility was measured using a speeded evaluative categorization task. Behavioral measures were the amount of beer poured and drunk during a bogus taste test and the choice between a bottle of beer or water at the end of the experiment. In line with our hypothesis, the indirectly measured attitude towards beer predicted behavior during the taste test only when it was highly accessible. In contrast, this attitude was related to choice behavior irrespective of attitude accessibility. This study confirms that indirect attitude measures can be valuable predictors of alcohol-related behavior, but that it is sometimes necessary to take attitude accessibility into account.     

The sweet and the bitter of mammalian taste

The discovery of two families of mammalian taste receptors has provided important insights into taste recognition and taste perception. Recent studies have examined the receptors and signaling pathways that mediate sweet, bitter, and amino acid taste detection in mammals. These studies demonstrate that taste cells are selectively tuned to different taste modalities and clarify the logic of taste coding in the periphery.     

Pre-Treatment with Amifostine Protects against Cyclophosphamide-Induced Disruption of Taste in Mice

Cyclophosphamide (CYP), a commonly prescribed chemotherapy drug, has multiple adverse side effects including alteration of taste. The effects on taste are a cause of concern for patients as changes in taste are often associated with loss of appetite, malnutrition, poor recovery and reduced quality of life. Amifostine is a cytoprotective agent that was previously shown to be effective in preventing chemotherapy-induced mucositis and nephrotoxicity. Here we determined its ability to protect against chemotherapy-induced damage to taste buds using a mouse model of CYP injury. We conducted detection threshold tests to measure changes in sucrose taste sensitivity and found that administration of amifostine 30 mins prior to CYP injection protected against CYP-induced loss in taste sensitivity. Morphological studies showed that pre-treatment with amifostine prevented CYP-induced reduction in the number of fungiform taste papillae and increased the number of taste buds. Immunohistochemical assays for markers of the cell cycle showed that amifostine administration prevented CYP-induced inhibition of cell proliferation and also protected against loss of mature taste cells after CYP exposure. Our results indicate that treatment of cancer patients with amifostine prior to chemotherapy may improve their sensitivity for taste stimuli and protect the taste system from the detrimental effects of chemotherapy.     

Expression of T1Rs and gustducin in palatal taste buds of mice

The palatal region of the oral cavity in rodents houses 100-300 taste buds and is particularly sensitive to sweet and umami compounds; yet, few studies have examined the expression patterns of transduction-related molecules in this taste field. We investigated the interrelationships between members of the T1R family and between each T1R and gustducin in palatal taste buds. Similar to lingual taste buds, T1R1 and T1R2 are generally expressed in separate palatal taste cells. In contrast to lingual taste buds, however, T1R2 and T1R3-positive palatal taste cells almost always coexpress gustducin, suggesting that sweet taste transduction in the palate is almost entirely dependent on gustducin. T1R1-positive palate taste cells coexpress gustducin about half the time, suggesting that other G proteins may contribute to the transduction of umami stimuli in this taste field.     

FXYD6, a Na,K-ATPase regulator, is expressed in type II taste cells

Taste buds contain three types of taste cells. Each type can respond to taste stimulation, and type II and III taste cells are electrically excitable. However, there are differences between the properties of type II and III taste cells. In this study, we found that Fxyd6, an Na,K-ATPase regulator gene, is expressed in type II taste cells in the taste buds of mice. Double-labeled in situ hybridization analysis showed that Fxyd6 was coexpressed with transient receptor potential cation channel, subfamily M, member 5 (Trpm5), a critical component of the sweet, bitter, and umami taste signal transduction pathways and that it was specifically expressed in type II taste cells. We also found that taste cells frequently coexpressed Fxyd6 and Na,K-ATPase β1. These results indicate the presence of an inherent mechanism that regulated transmembrane Na(+) dynamics in type II taste cells.