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Chemotransduction in Necturus taste buds, a model for taste processing.

The taste bud in Necturus serves as a good model for taste mechanisms in vertebrates. The large size of taste cells and relative accessibility of the tissue for detailed electrophysiological and ultrastructural studies makes this species well-suited for studying taste transduction. Important features of taste transduction that have been learned from investigations in Necturus are that voltage-gated potassium channels are preferentially distributed on the apical membrane of taste cells; voltage-gated potassium channels allow K ions to enter the cell when taste buds are stimulated with K salts; some chemical stimuli act by closing K channels, thereby eliciting depolarizing receptor potentials in taste cells. Many of these findings have been confirmed and extended in other animals, including mammals. Furthermore, recent evidence from experiments in Necturus suggests that there is a considerable degree of synaptic coupling among taste cells. This synaptic coupling could form the basis for signal processing and integration in the peripheral sensory organs of taste, the taste buds.

Animals

Mixtures of substances with similar tastes. A test of a psychophysical model of taste mixture interactions.

When substances of similar taste are mixed, the mixture can show suppression or synergism. That is, the perceived intensity of the mixture can be less than or greater than the sum of the perceived intensities of the components. In the present study, these departures from simple additivity could be predicted from the psychophysical functions relating tast intensity to stimulus concentration of the unmixed components. Psychophysical functions are said to show compression when successive increments in concentration produce progessively smaller increments in perceived intensity and to show expansion when successive increments in concentration produce progressively larger increments in perceived intensity. Suppression resulted from mixtures of substances with compressed psychophysical functions, and synergism resulted from mixtures of substances with expanded functions.

Adult

A conceptual model of taste receptors.

Of all the senses, that of taste is perhaps the hardest to define and quantify and elucidation of the underlying mechanisms is unrespondingly difficult. This article describes a conceptual model--at the molecular level--for the four basic taste modalities, using apparent specific volume as a fundamental parameter. It also considers possible practical applications.

Humans

A taste aversion model of drug discrimination learning: training drug and condition influence rate of learning, sensitivity and drug specificity.

A model of drug discrimination based on a lithium chloride (LiCl) flavour aversion was described and examined. Mildly thirsty rats were presented daily with 4 ml of a distinctly flavoured solution which was followed on 50% of the days by an IP injection of LiCl. Prior to the flavour presentation, the rats were injection SC with saline or a training drug (0.04 mg/kg fentanyl or 20 mg/kg pentobarbital) to signal whether LiCl would follow. Almost all rats eventually exhibited stable behaviour that involved drinking most or all of the fluid when it was not to be followed by LiCl and little or no drinking when it was. Such discrimination occurred regardless of whether drug predicted LiCl (learned-discomfort) or predicted no LiCl (learned-safety). However, with fentanyl there were clear differences between rats trained with drug under learned-safety and under learned-discomfort conditions for 1) the rate of acquisition of stable performance as a function of LiCl dose, 2) generalization of the training dose to a test dose that was lower, and 3) elicitation of fentanyl responses by pentobarbital. These findings, together with indications that such effects did not always occur with pentobarbital as the training drug, were discussed from theoretical and practical perspectives.

Animals

A model for the stimulation of taste receptor cells by salt.

A taste cell mucosal surface is regarded as a planar region containing bound anionic sites and openings to ionic channels. It is assumed that the bulk aqueous properties of the exterior phase are not continuous with the surface but terminate at a plane near the surface. The region between the (Stern) plane and the membrane is regarded as having a lower dielectric constant than bulk water. This fact admits the possibility of ion pair formation between fixed sites and mobile cations. Mobile ion pairs entering the region may also bind to a fixed anionic site. Thus, it is assumed that mobile cations and ion pairs are potential determining species at the surface. Binding cations neutralizes surface charges, whereas binding mobile ion pairs does not. This competition accounts for the observed anion effect on stimulation of tast receptors by sodium salts. The potential profile is constructed by superimposing the phase boundary potentials with an ionic diffusion potential across the membrane. The model accounts for the anion effect on receptor potential, pH effects, the reversal of polarity when cells are treated with FeCl3, and the so-called "water reponse," depolarization of the taste cell upon dilution of the stimulant solution below a critical lower limit. The proposed model does not require both bound cationic and anionic receptors, and further suggests that limited access to a Stern-like region continuous with membrane channels may generally serve to control transport of ions.

Acetates

Physicochemical studies of taste reception. III. Interpretation of the water response in taste reception.

The model membrane composed of a Millipore filter paper and the total lipids from bovine tongue epithelium or phosphatidylcholine from egg yolk simulated well the water response of a living taste cell, The water response observed with the model membrane adapted to various salt solutions was interpreted in terms of changes in electric potential at the membrane-solution interface, i.e. the water response was attributed to the e.m.f. change produced by diffusion of the electrolytes dissolved in (or adsorbed on) the membrane surface into the bulk solution. The water response of the frog tongue was also investigated by measuring the neural response of the glossopharyngeal nerve. The results obtained were consistent with the mechanism proposed in the present paper. The response of the frog to Ca2+ was examined under the condition where the water response was suppressed, and it was concluded that the water response of the frog is different from the response to Ca2+.

Animals

A review of sweet taste potentiation brought about by divalent oxygen and sulfur incorporation.

The plethora of high-potency sweetener research has allowed the construction of important structure-taste relationships. In light of new structure-taste relationships, it is instructive to review sweet taste potentiation brought about by divalent oxygen and sulfur incorporation. The taste of sulfur-containing organic compounds was reviewed in Japanese by Yasuo Ariyoshi in 1977. Several new representative examples of sweet taste potentiation and taste dichotomy (sweet and bitter) found within similar classes of oxygen- and sulfur-containing organic compound: amides, dipeptides, ureas, sulfamates, sulfonamides, oximes, sugars, dihydroisocoumarins, and others are reviewed. Special attention is given to the thioethers and thioureas in sulfamates, dipeptides, aryl ureas, and hybrid dipeptide ureas. The most notable contributions have arisen from the work of Nofre and Tinti at Université Claude Bernard in Lyons, France. A common trend emerges with certain sweeteners when a carbon atom is strategically replaced by sulfur or oxygen atoms. The net result is an increase in the sweetness two- to tenfold. With saccharins, the usual bitter, metallic taste is removed. Sweet taste receptor models that have been published are mainly based on the original Shallenberger and Acree model of the glucophores AH-B with contributions from Kier (AH-B-X). AH is a proton donor group, B is a proton acceptor group, and X is some hydrophobic group. All of the models have overlooked the contributions of divalent sulfur (often in place of oxygen) in bringing about sweetness potentiation. There is no precedence for localizing the energy-minimized structures of sulfur-containing sweeteners in a binding mode that includes sulfur. These sulfur potentiation loci are analyzed and illustrated in a computer-generated sweetener model to show the specific region in which sulfur is being "recognized" as a potentiating feature.

Humans

Concept of neuron types in gustation in the rat.

1. In taste neurophysiology, from Pfaffmann's (49, 50) pioneering work until the present, the possibility of types of neurons corresponding in some sense with the "primary" taste qualities of Henning (33) has been entertained: recently types of gustatory neurons in peripheral nerves have been established according to which of the four classical stimuli is the "best stimulus." However, considerable variation occurs in the response profiles within neurons classified as belonging to the same type. The purpose of this research is to determine, using mathematical techniques where appropriate, if the within-type variation is spurious or, instead, indicates the absence of a typology of taste neurons. The data used were counts of the spike discharges of 50 individual taste neurons in the nucleus of the solitary tract of the rat, evoked by 32 diverse chemical stimuli. 2. Using as input the matrix of Pearson r correlation coefficients calculated for the responses of all pairings of neurons to all stimuli, multidimensional scaling analysis revealed a two-dimensional space in which no clear groupings of neurons occurred. 3. In a hierarchical cluster analysis of the neuron response profile similarities, no evidence of grouping was found, suggesting a more-or-less continuous variation among neurons. 4. When the organization of the 32 stimuli utilized was studied by the same techniques, no clear evidence for stimulus types was found, although the possibility of two stimulus types--"sweet" and "nonsweet"--was raised. 5. Construction of a joint neuron-stimulus space supported a spatial model of taste neuron-stimulus interaction, while analysis of the number and pattern of high correlations among neurons--even after allowance for attenuation due to measurement error--failed to support the notion of types of taste neurons with identical response profiles. 6. Aspects of the logical role of types of neurons in gustatory coding were discussed, and the results and methods of the present investigation were related to classification schemes for neurons in general. Suggestions for a formal taxonomy of neurons were given. 7. It should be emphasized that the present study and conclusions are of second-order, CNS neurons, whereas the studies advocating the presence of neurons types were of peripheral neurons. Taken together, the implication to be drawn from these studies is that if neural types do exist in peripheral taste nerves, the typology is lost at the first synapse and is thus unavailable to the CNS for coding purposes, at least in the rat.

Animals

Model for the dynamic responses of taste receptor cells to salty stimuli. I. Function of lipid bilayer membranes.

The dynamic response of the lipid bilayer membrane is studied theoretically using a microscopic model of the membrane. The time courses of membrane potential variations due to monovalent salt stimulation are calculated explicitly under various conditions. A set of equations describing the time evolution of membrane surface potential and diffusion potential is derived and solved numerically. It is shown that a rather simple membrane such as lipid bilayer has functions capable of reproducing the following properties of dynamic response observed in gustatory receptor potential. Initial transient depolarization does not occur under Ringer adaptation but does under water. It appears only for comparatively rapid flows of stimuli, the peak height of transient response is expressed by a power function of the flow rate, and the membrane potential gradually decreases after reaching its peak under long and strong stimulation. The dynamic responses in the present model arise from the differences between the time dependences in the surface potential phi s and the diffusion potential phi d across a membrane. Under salt stimulation phi d cannot immediately follow the variation in phi s because of the delay due to the charging up of membrane capacitance. It is suggested that lipid bilayer in the apical membrane is the most probable agency producing the initial phasic response to the stimulation.

Animals

Gustatory neural coding in the monkey cortex: stimulus intensity.

1. We analyzed the activity of single neurons in gustatory cortex of alert cynomolgus monkeys in response to a range of stimulus intensities. Chemicals were deionized water, fruit juice, and several concentrations of the four prototypical taste stimuli: 10(-3)-1.0 M glucose, 10(-3)-1.0 M NaCl, 10(-4)-3 x 10(-2) M HCl, and 10(-5)-3 x 10(-3) M quinine HCl. 2. Taste-evoked responses could be recorded from a cortical gustatory area that measured 2.5 mm in its anteroposterior extent, 6.0 mm dorsoventrally, and 3.0 mm mediolaterally. Taste-responsive cells constituted 62 (3.7%) of the 1,661 neurons tested. Nongustatory cells gave responses associated with mouth movement (10.1%), somatosensory stimulation (2.2%), and approach or anticipation (0.9%). 3. Intensity-response functions were determined across 62 gustatory neurons. Neural thresholds for each stimulus quality conformed well to human psychophysical thresholds. Mean discharge rate was a direct function of stimulus concentration for glucose, NaCl, and quinine HCl. The most effective of the basic stimuli was glucose. 4. Power function exponents were calculated from the responses of neural subgroups most responsive to each basic stimulus. Those for glucose, NaCl, and quinine were within the range of psychophysically derived values. Thus the perceived intensity of each basic quality is presumably based on the activity of the appropriate neural subgroup rather than on the mean activity of all taste cells. 5. The mean breadth-of-tuning (entropy) coefficient for 62 gustatory neurons was 0.65 (range, 0.00-0.98). 6. There was no clear evidence of chemotopic organization in the gustatory cortex. 7. An analysis of taste quality indicated that sweet stimuli evoked patterns of activity that were clearly distinct from those of the nonsweet chemicals. Among the latter group, NaCl was differentiable from HCl and quinine HCl, whose patterns were closely related. 8. The response characteristics of cortical taste cells imply gustatory thresholds and intensity-response functions for the nonhuman primate that conform well to those reported in psychophysical studies of humans, reinforcing the value of this neural model for human taste intensity perception.

Action Potentials

Salt taste adaptation: the psychophysical effects of adapting solutions and residual stimuli from prior tastings on the taste of sodium chloride.

The paper reviews how adaptation to sodium chloride, changing in concentration as a result of various experimental procedures, affects measurements of the sensitivity, intensity, and quality of the salt taste. The development of and evidence for the current model that the salt taste depends on an adaptation level (taste zero) determined by the sodium cation concentration is examined and found to be generally supported, despite great methodological complications. It would seem that lower adaptation levels elicit lower thresholds, higher intensity estimates, and altered quality descriptions with predictable effects on psychophysical measures.

Adaptation, Physiological

Gustatory neural coding in the monkey cortex: L-amino acids.

1. Single-neuron activity in the primary gustatory cortex of the alert cynomolgus monkey (Macaca fascicularis) was analyzed in response to a range of taste stimuli. Tastants included the four prototypical stimuli (glucose, NaCl, HCl, and quinine), fruit juice, and 12 amino acids selected for their chemical characteristics, nutritional significance, and biological importance, as well as for the availability of human psychophysical data on their perceived qualities. 2. Taste-evoked responses could be recorded from a cortical area that measured 3.5 mm in its anteroposterior extent, 2.0 mm mediolaterally, and 6.0 mm dorsoventrally. Gustatory cells constituted 4.8% of the 1,129 neurons tested. Nongustatory cells gave responses associated with mouth movements (11.1%), somatosensory stimulation (3.8%), approach or anticipation of the taste stimulus (2.2%), and tongue extension (0.4%). 3. The most effective taste stimuli were those with qualities that humans describe as salty or sweet: NaCl, monosodium glutamate, glucose, proline, glycine, and fruit juice. The least effective tastants were those rated bitter or insipid: tyrosine, tryptophan, phenylalanine, and leucine. Accordingly, 79% of the gustatory neurons responded best to glucose (46%) or NaCl (33%) among the basic stimuli; only 19% responded best to quinine (13%) or HCl (6%). One cell (2%) responded exclusively to fruit juice. 4. Cortical gustatory neurons showed a moderate breadth of sensitivity, with a mean breadth of tuning coefficient of 0.71 across 54 cells. There was no evidence of chemotopic organization in the taste cortex. 5. The taste quality of each stimulus was inferred from the relative similarity of the profiles they evoked. The clearest distinction among stimuli was between those that humans characterize as sweet versus those with other qualities. Several amino acids that have dominant sweet (glycine and proline), salty (arginine and monosodium glutamate), sour (tryptophan), or bitter (phenylalanine) components to humans evoked activity profiles that were associated with those of the appropriate prototypical stimuli. Others (cysteine and lysine) were not closely related to any single prototype. 6. Conclusions based on the responses of cortical cells in the monkey are in close agreement with those that derive from human psychophysical studies of L-amino acids, reinforcing the value of this neural model for human taste perception.

Amino Acids

Specificity of mono- and divalent salt transduction mechanisms in frog gustation evidenced by cobalt chloride treatment.

1. Discrimination among stimuli with similar physical properties represents a formidable problem in sensory neurophysiology. The differential effect of cobalt chloride treatment on gustatory responses to monovalent and divalent salts may help to explain aspects of how the frog gustatory system encodes these stimuli. 2. Gustatory neural responses recorded from the glossopharyngeal nerve to divalent stimuli (CaCl2 and MgCl2) were inhibited by CoCl2 treatment, whereas monovalent responses (NaCl and KCl) were greatly augmented. Both effects were highly significant and completely reversible. 3. Intracellular recordings from the gustatory receptor cells, which synaptically initiate the impulses in the glossopharyngeal afferents, imply that these neural events are not a simple reflection of the receptor potential magnitude. Monovalent receptor potentials magnitudes (millivolts of depolarization) were enhanced by cobalt chloride, but receptor potentials to divalent stimuli were not inhibited. Rather they were either unaffected (MgCl2) or augmented (CaCl2). 4. Membrane resistance change during salt stimulation with cobalt chloride treatment followed the qualitative pattern observed with the neural response. Membrane resistance (in megohms) of the receptor cell was greater for divalent stimuli with cobalt treatment compared with divalent stimuli alone. Membrane resistance changes for monovalent stimuli were less with cobalt treatment compared with monovalent stimuli alone. These observations indicate that the glossopharyngeal neural response is not a simple reflection of the magnitude of the receptor potential but must be considered in conjunction with membrane resistance as an indicator of synaptic transmission. 5. These data were interpreted in terms of leading models of salt taste transduction, i.e., adsorption theories, phase boundary theories, and the direct penetration theories. Relevant mechanistic considerations for salt taste transduction in the frog include binding by divalents to membrane surface changes and amiloride-sensitive monovalent cation channels. It was concluded that the surface potential alone was not a critical variable in the mechanism of cobalt chloride alteration of salt responses.

Afferent Pathways

The cell biology of vertebrate taste receptors.

New technologies in neurophysiology and ultrastructural research are bringing about rapid advances in our understanding of taste, particularly at the cellular level. The model of chemosensory processing in the taste bud presented here can now be explored in great detail. The synaptic organization of the taste bud indicates a potential for intriguing peripheral integrative mechanisms, including cross-talk between taste cells, summation of chemoreceptor responses by interneurons (basal cells) in the taste bud, and centrifugal control of taste buds via efferent input from the CNS. Figure 2 summarizes these findings. The existence of voltage-gated ionic channels on taste cells and their unequal distribution in apical and basolateral membrane suggests mechanisms for chemosensory transduction: A primary event in the transduction process for many taste stimuli is likely to be the closure of apical potassium channels, thus leading to a depolarizing receptor potential. The closure of these apical potassium channels is probably mediated via cyclic nucleotides or intracellular Ca2+.

Animals