Single Taste Research Articles

Influence of Response Variability on the Coding Performance of Central Gustatory Neurons

We explored how variability in responding to taste stimuli could impact the signaling of taste quality information by neuron types and individual cells in the nucleus of the solitary tract. One hundred sixty-two neurons recorded from anesthetized rats were grouped using multivariate analysis of taste responses to the following (in m): 0.5 sucrose, 0.1 NaCl, 0.01 HCl, and 0.01 quinine-HCl. Neurons fell into one of three groups corresponding to cell types that responded optimally to sucrose, NaCl, or HCl. A statistical model was used to examine whether responses observed among neurons within each group could be correctly attributed to the optimal stimulus or another tastant on the basis of spike count. Results revealed poor classification performance in some cases attributable to wide variations in the sensitivities of neurons that compose a cell type. This outcome leads us to question whether neuron types could faithfully encode a single taste quality. We then theoretically explored whether a hypothetical observer of individual neurons could discriminate between spiking rates to different tastants during the first second of stimulus processing. Spike rate was found to be an unreliable predictor of stimulus quality for each neuron tested. However, additional analyses suggested that taste stimuli could be identified by a reader that attends to the relative spiking activities of different kinds of neurons in parallel. Rather than assigning meaning to individual neurons or categories of them, central gustatory circuits may signal quality information using a strategy that involves the relative activities of neurons with different sensitivities to tastants.

Expression of purinergic receptors in mouse taste buds

Each taste bud (a taste sensor) in mouse tongues consists of ∼50 taste bud cells (TBCs) that express various neurotransmitter receptors on their basolateral membranes. We investigated the expression of ATP receptor subtypes with neurophysiological, molecular biological, and immunohistochemical techniques. Here we show that TBCs expressed P2X2, P2X7 and P2Y1 subtypes. These results showed that ATP probably released from TBCs or taste nerves during taste responses could finely regulate the functions of neighbouring TBCs by stimulating their heterogeneous ATP receptor subtypes. Such interactions among TBCs may form cell networks within single taste buds and may process taste information on the tongue.

Mass Customization vs. Mass Production: Variety and Price Competition

We study competition between two multiproduct firms with distinct production technologies in a market where customers have heterogeneous preferences on a single taste attribute. The mass customizer (MC) has a perfectly flexible production technology and thus can offer any variety within a product space, represented by Hotelling's linear city. The mass producer (MP) has a more focused production technology and therefore offers a finite set of products in the same space. The MP can invest in more flexible technology, which reduces its cost of variety and hence allows it to offer a larger set of products; in the extreme, the MP can emulate the MC's technology and offer infinite variety. The firms simultaneously decide whether to enter the market, and the MP chooses its degree of product-mix flexibility on entry. Next, the MP designs its product line—i.e., the number and position of its products—the MC's perfectly flexible technology makes this unnecessary. Finally, both firms simultaneously set prices. We analyze the subgame-perfect Nash equilibrium in this three-stage game, allowing firm-specific fixed and variable costs that together characterize their production technology. We find that an MP facing competition from an MC offers lower product variety than an MP monopolist to reduce the intensity of price competition. We also find that the MP can survive this competition, even if it has higher fixed cost of production technology, higher marginal cost of production, or both.

Electrophysiologically identified subpopulations of taste bud cells

The heterogeneous population of mammalian taste cells includes several cellular subtypes specializing in distinct physiological functions. They are poorly understood at the single cell level because the available physiological data have generally been obtained from unidentified taste cells. We recorded them from individual taste cells isolated from circumvallate, foliate, and fungiform papilla of the mouse, employing the patch clamp technique, and tried to elucidate whether universal electrophysiological criteria may be established for the identification of functionally different cellular subpopulations. It was found that irrespective of the papillae type, most (∼96%) of robust taste cells could be categorized into three distinct subgroups on the basis of families of whole-cell (WC) currents exhibited in response to membrane polarization. The validity of this quite simple criterion was further confirmed by using different voltage clamp protocols, ion substitutions, and channel blockers to record different ionic currents, including voltage-gated (VG) Ca 2+, inward-rectifying K +, and hyperpolarization-activated currents. Given that our findings are based on the statistically significant number of recordings, we believe that the electrophysiological identification of taste cells presented here may be effective for further studies on single taste cell physiology, including taste transduction.

Elucidating coding of taste qualities with the taste modifier miraculin in the common marmoset

To investigate the relationships between the activity in different types of taste fibers and the gustatory behavior in marmosets, we used the taste modifier miraculin, which in humans adds a sweet taste quality to sour stimuli. In behavioral experiments, we measured marmosets’ consumption of acids before and after tongue application of miraculin. In electrophysiological experiments responses of single taste fibers in chorda tympani and glossopharyngeal nerves were recorded before and after tongue application of miraculin. We found that after miraculin marmosets consumed acids more readily. Taste nerve recordings showed that after miraculin taste fibers which usually respond only to sweeteners, S fibers, became responsive to acids. These results further support our hypothesis that the activity in S fibers is translated into a hedonically positive behavioral response.

Taste Receptor Cells Responding with Action Potentials to Taste Stimuli and their Molecular Expression of Taste Related Genes

Recent molecular biological studies have revealed many molecular aspects of taste transduction in receptor cells for each taste categories which are referred to as salty, sweet, sour, bitter and umami in human respectively. (Lindemann, 2001; Gilbertson and Boughter, 2003). For example, ion channels such as ENaC, ASIC and HCN mediate salty and sour taste and G-protein-coupled receptors such as T1Rs and T2Rs play a key role in sweet, bitter and umami taste. However, there is little evidence for involvements of these molecules in taste reception and transduction at the cellular level. It is necessary to examine both molecular and physiological properties in single taste receptor cell. In this study, by use of loose patch recording technique combined with single cell multiplex RT–PCR, we characterized single taste cells by their responses to four basic taste stimuli and expression of taste-related molecules.

Mass Customization Versus Mass Production: Variety and Price Competition

We study competition between two multi-product firms with distinct production technologies in a market where customers have heterogeneous preferences on a single taste attribute. The mass customizer (MC) has a perfectly flexible production technology, thus can offer any variety within a product space, represented by Hotelling's (1929) linear city. The mass producer (MP) has a more focused production technology, and therefore, it offers a finite set of products in the same space. MP can invest in more flexible technology, which reduces its cost of variety and hence allows it to offer a larger set of products; in the extreme,MP can emulate MC's technology and offer infinite variety. The firms simultaneously decide whether to enter the market, and MP chooses its degree of product-mix flexibility upon entry. Next, MP designs its product line, i.e., the number and position of its products; MC's perfectly flexible technology makes this unnecessary. Finally, both firms simultaneously set prices. We analyze the sub-game perfect Nash equilibrium in this three-stage game, allowing firm-specific fixed and variable costs that together characterize their production technology. We find that an MP facing competition from an MC offers lower product variety compared to an MP monopolist, in order to reduce the intensity of price competition. We also find that MP can survive this competition even if it has higher fixed cost of production technology or higher marginal cost of production or both.

Modulation of taste peripheral signal through interpapillar inhibition in hamsters

Single taste buds from fungiform papillae were iontophoretically stimulated with chemicals filling glass microelectrodes while a single unit was recorded in the taste pore of a neighbor papilla. High signal-to-noise ratio responses were observed in the recorded papilla as antidromic action potentials. These responses were possibly modulated by the simultaneous stimulation of another adjacent papilla. A decrease in the frequency of firing and/or both decrementing spikes were observed during such dual papillae stimulations. These inhibitory effects were not modified by the section of the chordo-lingual nerve, suggesting the tongue is able to process the gustatory information thanks to interpapillar negative feedback, prior to transmitting the signal to the central nervous system. Branched chorda tympani fibers can account for responses observed for single papillae stimulations; inhibitions and decrementing spikes may suggest the contribution of another mechanism of interaction between two different single fibers.

Voltage-gated channels involved in taste responses and characterizing taste bud cells in mouse soft palates

Taste bud cells (TBCs) on soft palates differ from those on tongues in innervation and chemosensitivity. We investigated voltage-gated channels involved in the taste responses of TBCs on mouse soft palates under in-situ tight-seal voltage/current-clamp conditions. Under the cell-attached mode, TBCs spontaneously fired action currents, which were blocked by application of 1 μM TTX to TBC basolateral membranes. Firing frequencies increased in response to taste substances applied to TBC receptor membranes. Under the whole-cell clamp mode, as expected, TBCs produced various voltage-gated currents such as TTX-sensitive Na + currents ( I Na), outward currents ( I out) including TEA-sensitive and insensitive currents, inward rectifier K + currents ( I ir), and Ca 2+ currents including T-type, P/Q-type, and L-type Ca 2+ currents. We classified TBCs into three types based on the magnitude of their voltage-gated Na + currents and membrane capacitance. HEX type (60% of TBCs examined) was significantly larger in Na + current magnitude and smaller in membrane capacitance than LEX type (23%). NEX type (17%) had no Na + currents. HEX type was equally distributed within single taste buds, while LEX type was centrally distributed, and NEX type was peripherally distributed. There were correlations between these electrophysiological cell types and morphological cell types determined by three-dimensional reconstruction. The present results show that soft palate taste buds contain TBCs with different electrophysiological properties, and suggest that their co-operation is required in taste transduction.

(+)-(S)-alapyridaine--a general taste enhancer?

N-(1-Carboxyethyl)-6-hydroxymethyl-pyridinium-3-ol inner salt (alapyridaine), recently identified in heated sugar/amino acid mixtures as well as in beef bouillon, has been shown to exhibit general taste-enhancing activities, although tasteless on its own. Differing from other taste enhancers reported so far, racemic (R/S)-alapyridaine and, to an even greater extent (+)-(S)-alapyridaine, the physiologically active enantiomer, are able to enhance more than one basic taste quality. The threshold concentrations for the sweet taste of glucose and sucrose, for the umami taste of monosodium L-glutamate (MSG) and guanosine-5'-monophosphate (GMP), as well as the salty taste of NaCl, were significantly decreased when alapyridaine was present. In contrast, perception of the bitter tastes of caffeine and L-phenylalanine, as well as of sour-tasting citric acid, was unaffected. Furthermore, alapyridaine was shown to intensify known taste synergies such as, for example, the enhancing effect of L-arginine on the salty taste of NaCl, as well as that of GMP on the umami taste of MSG. The activity of (+)-(S)-alapyridaine could be observed not only in solutions of single taste compounds, but also in more complex tastant mixtures; for example, the umami, sweet and salty taste of a solution containing MSG, sucrose, NaCl and caffeine was significantly modulated, thus indicating that alapyridaine is a general taste enhancer.

One Taste Per Cell, but a Common Signaling Cascade

There are controversial views of how mammals distinguish the five taste flavors--bitter, sweet, umami (amino acid), salty, and sour. One model asserts that an individual taste receptor cell expresses only one type of taste receptor and therefore only recognizes and transduces signals in response to a single flavor. Alternatively, a single taste receptor cell could express different taste receptors and thus respond broadly to different taste stimuli, possibly through multiple signaling pathways. A study by Zhang et al. favors a separation of taste perception at the cellular level. However, the three different receptor types that recognize sweet-, umami-, and bitter-tasting ligands all impinge on a common signaling cascade that involves phospholipase Cβ2 (PLCβ2) and a transient receptor potential-like channel (TRPM5), both of which have been previously linked to taste transduction. The authors show that both molecules are coexpressed in taste cell receptors of mice. Genetically altered mice lacking both molecules failed to detect sweet, umami, and bitter stimuli. Neurons that normally propagate signals from activated taste cells to the brain failed to generate action potentials in response to any of theses taste modalities. Only bitter taste perception was rescued when PLCβ2 expression was restored in the subpopulation of cells that expressed the bitter taste receptor. Thus, sweet, umami, and bitter tastes are recognized by distinct cell populations, but converge on a common transduction channel through PLCβ2 to trigger a taste response. Y. Zhang, M. A. Hoon, J. Chandrashekar, K. L. Mueller, B. Cook, D. Wu, C. S. Zuker, N. J. P. Ryba, Coding of sweet, bitter, and umami tastes: Different receptor cells sharing similar signaling pathways. Cell 112 , 293-301 (2003). [Online Journal]

One Taste Per Cell, but a Common Signaling Cascade

There are controversial views of how mammals distinguish the five taste flavors--bitter, sweet, umami (amino acid), salty, and sour. One model asserts that an individual taste receptor cell expresses only one type of taste receptor and therefore only recognizes and transduces signals in response to a single flavor. Alternatively, a single taste receptor cell could express different taste receptors and thus respond broadly to different taste stimuli, possibly through multiple signaling pathways. A study by Zhang et al. favors a separation of taste perception at the cellular level. However, the three different receptor types that recognize sweet-, umami-, and bitter-tasting ligands all impinge on a common signaling cascade that involves phospholipase Cβ2 (PLCβ2) and a transient receptor potential-like channel (TRPM5), both of which have been previously linked to taste transduction. The authors show that both molecules are coexpressed in taste cell receptors of mice. Genetically altered mice lacking both molecules failed to detect sweet, umami, and bitter stimuli. Neurons that normally propagate signals from activated taste cells to the brain failed to generate action potentials in response to any of theses taste modalities. Only bitter taste perception was rescued when PLCβ2 expression was restored in the subpopulation of cells that expressed the bitter taste receptor. Thus, sweet, umami, and bitter tastes are recognized by distinct cell populations, but converge on a common transduction channel through PLCβ2 to trigger a taste response. Y. Zhang, M. A. Hoon, J. Chandrashekar, K. L. Mueller, B. Cook, D. Wu, C. S. Zuker, N. J. P. Ryba, Coding of sweet, bitter, and umami tastes: Different receptor cells sharing similar signaling pathways. Cell 112, 293-301 (2003). [Online Journal]

THE BITTER TASTE OF GREENS

Bitter flavours often mean that something is poisonous. But most plants are bitter tasting, so it is important for plant eaters to distinguish between bitter flavours that are toxic, and those that are not. Until now, its has been readily accepted that animals could not tell bitter tastes apart when individual bitter taste receptors sent messages to one part of the brain, or a single receptor was responsible for detecting both flavours. This study by John Glendinning and colleagues, Adrienne Davis and Sudha Ramaswamy, contests these assumptions.The experiments use taste habituation as a model system to determine whether bitterness receptors on the mouthparts of Manduca sextacaterpillars can discriminate between five bitter tasting diets: salicin,caffeine, aristolochic acid, and two bitter tasting plant extracts. The caterpillars have four different classes of taste receptor. Each receptor houses many different taste cells, but only one cell in each receptor responds to bitterness. These cells respond with varying efficacies to any given zest.Caterpillars were first fed with a training diet containing salicin. When they no longer rejected the food, they were considered to have habituated to the chemical. The larvae were then given an edible control-disc, followed by a distasteful bitter test-disc, and munching rates were monitored throughout. If the caterpillars rejected the new bitter flavour after habituation, then they must be able to distinguish between salicin and the new flavour.After habituation, the caterpillars no longer showed their usual aversion to caffeine. But the caterpillars still rejected the bitter flavours of aristolochic acid, and the two plant extracts.When they looked at the way that the caterpillars responded to aristolochic acid, they realised that the neural mechanism was different from that used to encode the taste of the plant extracts. Discriminating the plant extracts relied on one cell responding to the extract, and a different cell responding to salicin. The team knew that the caterpillars have two receptors that both respond to aristolochic acid. They wondered about the relative importance of these receptors, so they surgically removed one of them. The ability to discriminate the aristolochic acid from salicin remained, so a single taste cell somehow managed to distinguish between the two flavours! The team already knew that some taste cells could signal the presence of two different bitter flavours as opposed to one, by sending distinct nerve signals for each flavour they detect. When the team measured the remaining taste cell's response to aristolochic acid, they found that this was indeed the case. The cell's response to aristolochic acid was very different from the signals it sent when recognising salicin. It now seems that caterpillars are equally able to discriminate tastes whether they are using two different taste cells or two pathways within one cell.The authors argue that bitter taste discrimination does not occur at the level of the receptor but at the central nervous system, which can respond selectively to different coding pathways. This has implications for future studies of taste processing, since it is still unknown whether the whole animal can sense different sub-tastes of bitterness. It seems we can learn still more from watching other animals eat their greens.

Dual actions of caffeine on voltage-dependent currents and intracellular calcium in taste receptor cells.

Although the numerous stimuli representing the taste quality of bitterness are known to be transduced through multiple mechanisms, recent studies have suggested an unpredicted complexity of the transduction pathways for individual bitter stimuli. To investigate this notion more thoroughly, a single prototypic bitter stimulus, caffeine, was studied by using patch-clamp and ratiometric imaging techniques on dissociated rat taste receptor cells. At behaviorally relevant concentrations, caffeine produced strong inhibition of outwardly and inwardly rectifying potassium currents. Caffeine additionally inhibited calcium current, produced a weaker inhibition of sodium current, and was without effect on chloride current. Consistent with its effects on voltage-dependent currents, caffeine caused a broadening of the action potential and an increase of the input resistance. Caffeine was an effective stimulus for elevation of intracellular calcium. This elevation was concentration dependent, independent of extracellular calcium or ryanodine, and dependent on intracellular stores as evidenced by thapsigargin treatment. These dual actions on voltage-activated ionic currents and intracellular calcium levels suggest that a single taste stimulus, caffeine, utilizes multiple transduction mechanisms.

Committee Report: Options for a Taste and Odor Standard

With increased public awareness of drinking water issues, water suppliers are under growing pressure to adhere to an acceptable standard of aesthetic quality. However, establishing a practical, feasible level of control for tastes and odors in drinking water is fraught with difficulties. A variety of chemical compounds can affect taste and odor, and the analytical methods available for detecting them vary in cost, effectiveness and ease of use. Taste and odor preferences are also subjective, and sensitivities to tastes and odors vary not only from customer to customer but for the same individual from day to day. The Taste and Odor Committee of AWWA's Water Quality Division reviewed existing taste and odor guidelines, from the US Environmental Protection Agency's 1979 guidance establishing secondary maximum contaminant levels to more recent regulatory actions regarding volatile organic chemicals and methyl tertiary butyl ether. In addition, the committee critiqued a range of possible regulatory options based on such criteria as chemical concentrations, frequency of occurrence, treatment techniques, and use of surrogates. The committee concluded that there was little possibility of establishing a single taste and odor standard that could apply equally to public perception of tap water quality nationwide. As an alternative, they proposed self‐regulation by the industry, through the creation of a quality program similar to the Partnership for Safe Water. Such a program could help improve the taste and odor quality of drinking water and, at the same time, eliminate the need for cumbersome regulatory standards or guidelines.

Rats Fail to Discriminate Quinine from Denatonium: Implications for the Neural Coding of Bitter-Tasting Compounds

Recent molecular findings indicate that many different G-protein-coupled taste receptors that bind with "bitter-tasting" ligands are coexpressed in single taste receptor cells in taste buds, leading to the prediction that mammals can respond behaviorally to structurally diverse "bitter" tastants but cannot discriminate among them. However, recent in situ calcium-imaging findings imply that rat taste receptor cells are more narrowly tuned to respond to bitter-tasting compounds than had been predicted from molecular findings, suggesting that these animals can discriminate among these chemicals. Using an operant conditioning paradigm, we demonstrated that rats cannot discriminate between two structurally dissimilar bitter compounds, quinine hydrochloride and denatonium benzoate, despite the fact that these tastants are thought to stimulate different taste receptor cells. These rats were nonetheless able to show concentration-dependent avoidance responses to both compounds in brief-access tests and to discriminate among other taste stimuli, including quinine versus KCl, denatonium versus KCl, and NaCl versus KCl. Importantly, the concentrations were varied in the discrimination tests to render intensity an irrelevant cue. We conclude that denatonium and quinine produce a unitary taste sensation, leaving open the likely possibility that other compounds fall into this class. Although a broader array of compounds needs to be tested, our findings lend support to the hypothesis that there is only one qualitative type of bitterness. These results also highlight the need to confirm predictions about the downstream properties of the gustatory system, or any sensory system, based on upstream molecular and biophysical events.

1C1100 マウス単一味蕾における味細胞応答の記録(14.化学受容,一般演題,日本生物物理学会第40回年会)

1C1100 マウス単一味蕾における味細胞応答の記録(14.化学受容,一般演題,日本生物物理学会第40回年会)

Neural networks distinguish between taste qualities based on receptor cell population responses.

Response features of taste receptor cell action potentials were examined using an artificial neural network to determine whether they contain information about taste quality. Using the loose patch technique to record from hamster taste buds in vivo we recorded population responses of single fungiform papillae to NaCl (100 mM), sucrose (200 mM) and the synthetic sweetener NC-00274-01 (NC-01) (200 microM). Features of each response describing both burst and inter-burst characteristics were then presented to an artificial neural network for pairwise classification of taste stimuli. Responses to NaCl could be distinguished from those to both NC-01 and sucrose with accuracies of up to 86%. In contrast, pairwise comparisons between sucrose and NC-01 were not successful, scoring at chance (50%). Also, comparisons between two different concentrations of NaCl, 0.01 and 0.005 M, scored at chance. Pairwise comparisons using only those features that relate to the inter-burst behavior of the response (i.e. bursting rate) did not hinder the performance of the neural network as both sweeteners versus NaCl received scores of 75--85%. Comparisons using features corresponding to each individual burst scored poorly, receiving scores only slightly above chance. We then compared the sweeteners with varying concentrations of NaCl (0.1, 0.01, 0.005 and 0.001 M) using only those features corresponding to bursting rate within a 1 s time window. The neural network was capable of distinguishing between NaCl and NC-01 at all concentrations tested; while comparisons between NaCl and sucrose received high scores at all concentrations except 0.001 M. These results show that two different taste qualities can be distinguished from each other based solely on the bursting rates of action potentials in single taste buds and that this distinction is independent of stimulation intensity down to 0.001 M NaCl. These data suggest that action potentials in taste receptor cells may play a role in taste quality coding.

Taste receptor cells that discriminate between bitter stimuli.

Recent studies showing that single taste bud cells express multiple bitter taste receptors have reignited a long-standing controversy over whether single gustatory receptor cells respond selectively or broadly to tastants. We examined calcium responses of rat taste receptor cells in situ to a panel of bitter compounds to determine whether individual cells distinguish between bitter stimuli. Most bitter-responsive taste cells were activated by only one out of five compounds tested. In taste cells that responded to multiple stimuli, there were no significant associations between any two stimuli. Bitter sensation does not appear to occur through the activation of a homogeneous population of broadly tuned bitter-sensitive taste cells. Instead, different bitter stimuli may activate different subpopulations of bitter-sensitive taste cells.

Optical recordings of taste responses from fungiform papillae of mouse in situ.

Single taste buds in mouse fungiform papillae consist of approximately 50 elongated cells (TBCs), where fewer than three TBCs have synaptic contacts with taste nerves. We investigated whether the non-innervated TBCs were chemosensitive using a voltage-sensitive dye, tetramethylrhodamine methyl ester (TMRM), under in situ optical recording conditions. Prior to the optical recordings, we investigated the magnitude and polarity of receptor potentials under in situ whole-cell clamp conditions. In response to 10 mM HCl, several TBCs were depolarized by approximately 25 mV and elicited action potentials, while other TBCs were hyperpolarized by approximately 12 mV. The TBCs eliciting hyperpolarizing receptor potentials also generated action potentials on electrical stimulation. A mixture of 100 mM NaCl, 10 mM HCl and 500 mM sucrose depolarized six TBCs and hyperpolarized another three TBCs out of 13 identified TBCs in a taste bud viewed by optical section. In an optical section of another taste bud, 1 M NaCl depolarized five TBCs and hyperpolarized another two TBCs out of 11 identified TBCs. The number of chemosensitive TBCs was much larger than the number of innervated TBCs in a taste bud, indicating the existence of chemosensitivity in non-innervated TBCs. There was a tendency for TBCs eliciting the same polarity of receptor potential to occur together in taste buds. We discuss the role of non-innervated TBCs in taste information processing.