Information processing in mammalian gustatory systems.

The taste system has multiple functions that are carried by three cranial nerves. It is now apparent that these functions cannot be accommodated by a single coding mechanism for taste quality. A current view emphasizes the likely existence of coding channels activated by specific sets of receptors.

Anion modulation of taste responses in sodium-sensitive neurons of the hamster chorda tympani nerve.

Beidler's work in the 1950s showed that anions can strongly influence gustatory responses to sodium salts. We have demonstrated "anion inhibition" in the hamster by showing that the chorda tympani nerve responds more strongly to NaCl than to Na acetate over a wide range of concentrations. Iontophoretic presentation of Cl- and acetate to the anterior tongue elicited no response in the chorda tympani, suggesting that these anions are not directly stimulatory. Drugs (0.01, 1.0, and 100 microM anthracene-9-carboxylate, diphenylamine-2-carboxylate, 4-acetamido-4'-isothiocyanatostilbene-2,2'-disulfonate, and furosemide) that interfere with movements of Cl- across epithelial cells were ineffective in altering chorda tympani responses to 0.03 M of either NaCl or Na acetate. Anion inhibition related to movements of anions across epithelial membranes therefore seems unlikely. The chorda tympani contains a population of nerve fibers highly selective for Na+ (N fibers) and another population sensitive to Na+ as well as other salts and acids (H fibers). We found that N fibers respond similarly to NaCl and Na acetate, with spiking activity increasing with increasing stimulus concentration (0.01-1.0 M). H fibers, however, respond more strongly to NaCl than to Na acetate. Furthermore, H fibers increase spiking with increases in NaCl concentration, but generally decrease their responses to increasing concentrations of Na acetate. It appears that anion inhibition applies to taste cells innervated by H fibers but not by N fibers. Taste cells innervated by N fibers use an apical Na+ channel, whereas those innervated by H fibers may use a paracellularly mediated, basolateral site of excitation.

Taste-responsive neurons and their locations in the solitary nucleus of the hamster.

The solitary nucleus (nucleus tractus solitarii), the first central relay for taste in mammals, was studied anatomically and physiologically in the golden hamster (Mesocricetus auratus). Activity of neurons to anterior tongue stimulation with sucrose, NaCl and KCl were extracellularly recorded. Electrolytic lesions or horseradish peroxidase deposits allowed subsequent localization of recording sites. Anterior tongue taste-responsive sites were restricted to a very small part of the rostral pole of the solitary nucleus, which is about 3% of the entire nucleus. Sites were confined to the rostral-central and rostral-lateral subdivisions of Whitehead, which contain a number of morphological cell types. Some chemotopic organization was seen with multi-unit recordings, with NaCl-selective sites concentrated rostrally and sucrose- and KCl-selective sites concentrated caudally. Sites with broad sensitivity were distributed throughout the gustatory region. Single neural units showing inhibition to taste stimuli, units highly reactive to all three stimuli, and units with high spontaneous rates were seen in the solitary nucleus, as well as units that responded very selectively and had low spontaneous rates. Single units with similar response profiles to sucrose, NaCl and KCl were not segregated to separate restricted locations within the taste-reactive region; their distributions overlapped. In the hamster, neurons in the anterior tongue taste region of the solitary nucleus process taste quality information in diverse ways. Highly reactive non-specific neurons, neurons that show inhibition, and neurons with high spontaneous rates are more frequently observed in the solitary nucleus than in the afferent input fibers of the chorda tympani nerve. The small region of the rostral pole enclosing taste-responsive neurons is complexly organized in relation to taste quality and contains a number of morphological cell types whose functional role in taste is not yet known.

Specificity of amiloride inhibition of hamster taste responses.

Amiloride, a blocker of epithelial sodium channels, was found to have significant effects on electrophysiological and behavioral taste responses in the golden hamster (Mesocricetus auratus). Recordings from the whole chorda tympani nerve showed that amiloride rapidly, reversibly, and competitively inhibited responses to NaCl applied to the anterior tongue. The apparent dissociation constant for amiloride binding, extrapolated to zero NaCl concentration, was 10 nM, a value comparable to estimates for various transporting tight epithelia. Recordings from single chorda tympani nerve fibers showed that 10 microM amiloride completely inhibited responses of Na-selective N fibers but had minimal effect on responses of electrolyte-sensitive H fibers, even though both types of fibers responded well to 0.1 M NaCl. Sucrose responses were not affected by amiloride. Addition of 100 microM amiloride to 0.1 M NaCl consistently increased consumption of NaCl in two-bottle drinking tests. These data suggest that one mechanism by which the taste of NaCl is sensed, which does not require adsorption or a second messenger, involves entry of Na+ into taste bud cells through an amiloride-blockable sodium channel. Taste bud cells utilizing this mechanism exclusively activate N fibers, which are involved in the control of NaCl intake. A different mechanism for the detection of NaCl and other electrolytes is utilized by taste bud cells that activate H fibers.

Opponent effects of quinine and sucrose on single fiber taste responses of the chorda tympani nerve.

Responses of single chorda tympani fibers to mixtures of taste stimuli were studied in the golden hamster (Mesocricetus auratus). Sucrose-best neurons showed significant suppression to quinine-sucrose mixtures compared to sucrose alone. Quinine may exert its effect as an opponent stimulus in the receptor cells at the second messenger level. This suppression may make bitter quinine more readily detected when embedded in mixtures with sweeteners.

Persistence of taste buds in denervated fungiform papillae.

Taste buds in hamster fungiform papillae persist in an atrophic state for as long as 330 days after chorda tympani denervation or 50 days after combined chorda tympani-lingual nerve resection. Although taste bud structure depends on innervation, there is no absolute neural requirement for taste bud survival.

Effects of chlorhexidine on human taste perception.

Chlorhexidine, a bis-cationic biguanide antiseptic, greatly reduces the perceived intensity of the salty prototype sodium chloride and may prove to be an important probe of mechanisms that underlie the human salty taste quality. Chlorhexidine, which tastes bitter, also reduces quinine hydrochloride taste intensity, but neither sweet sucrose nor sour citric acid is affected. Perceptual intensity rating and quality identification were measured for human subjects before and for 30 min following treatment with 1.34 mM chlorhexidine gluconate. In one experiment, test stimuli were the taste-quality prototypes; in a second experiment, stimuli were series of sodium, halide and sulfate salts. Experiment 1 showed a single 3-min chlorhexidine treatment resulted in reductions in taste intensity that persisted for at least 30 min. Experiment 2 showed a single 2-min chlorhexidine treatment reduced perceptual intensities of halide and sulfate salts except those with divalent cations. Chlorhexidine impaired identification of the salty quality and produced a bitter quality in nonbitter salts and impaired identification of the bitter quality of quinine, but not bitter salts. The specific effect of chlorhexidine on the bitterness of quinine suggests it may bind to the same receptor as quinine. The ability of chlorhexidine to specifically disrupt saltiness of a wide range of salts is consistent with proposed peripheral transduction mechanisms for the salty quality that involve transepithelial ion transport.

The role of sucrose-sensitive neurons in ingestion of sweet stimuli by hamsters.

The relationship between sweet preference and activity in sucrose-sensitive chorda tympani nerve fibers was investigated in hamsters (Mesocricetus auratus). Without exception, hamsters increased consumption of aqueous solutions of nonsweet 0.1 M NaCl, 0.001 M quinine-HCl, 0.01 M citric acid, 0.001 M dithiothreitol, 0.01 M pyridine, 0.01 M 2-phenylethanol, 0.005 M i-amyl acetate, 0.01 M vanillin, half-saturated 1-menthol and 0.033 mM capsaicin if they were made sweet by adding 0.5 M sucrose. Since sucrose activates chorda tympani S fibers, activity in these nerve fibers may be sufficient for increased preference. To determine if S-fiber activity is necessary for preference, equally preferred sweet stimuli were presented to the tongue while recording responses of single chorda tympani fibers. S fibers were clearly activated by 0.03 M sucrose, 0.001 M Na saccharin, 0.01 M D-phenylalanine, 0.1 M glycine, 0.005 M dulcin and 0.03 M Na 2-mercaptoethanesulfonate but not by 0.01 M Ca cyclamate and 0.003 M Na 3-nitrobenzenesulfonate. Ca cyclamate weakly activated H fibers and Na 3-nitrobenzenesulfonate weakly activated N fibers. Thus, S-fiber chorda tympani activity may be sufficient but not necessary for sweet preference, which may be influenced by activity in fibers of other taste nerves.

Analysis of polysaccharide taste in hamsters: behavioral and neural studies.

A series of studies was carried out in hamsters (Mesocricetus auratus) to determine whether polysaccharides have behavioral and neurophysiological characteristics that distinguish them from simple sugars. Behavioral studies utilized solutions of glucose, maltose, sucrose, Polycose, and glycogen in two-bottle preference tests and in tests of generalization of conditioned taste aversions. Multiunit and single-unit responses of the chorda tympani nerve were studied with the same stimuli. Neural responses to Polycose and glycogen were found to be generated primarily by ionic contaminants. Dialysis or deionization dramatically reduced electrophysiological responses, a result consistent with occurrence of Polycose and glycogen sensitivity in electrolyte-sensitive nerve fibers. Effects of treatment with the Na + -channel blocker amiloride and cross-adaptation were also consistent with neural responses generated by ionic contaminants. Hamsters showed strong preferences for the sugars and Polycose, a mixture of glucose polymers with alpha-1,4 linkages, and even stronger preferences for a glycogen preparation. Conditioned flavor aversions were established to glycogen, sucrose, and maltose, but no aversion was learned to 3.2% Polycose. The learned aversion to maltose partly generalized to glycogen and sucrose, but sucrose and glycogen did not cross-generalize. Deionization did not affect the preferences for Polycose and glycogen but removal of contaminants of mol.wt. < or = 7000 Da greatly reduced preference for glycogen. In conclusion, glycogen itself, after removal of low molecular weight contaminants, is a poor taste stimulus in hamsters, both behaviorally and neurophysiologically. However, Polycose is highly preferred by hamsters but gives little chorda tympani response after removal of ionic contaminants. In alert animals, the action of salivary amylase on polysaccharides may produce simpler, detectable taste stimuli.

The sense of taste: neurobiology, aging, and medication effects.

The sense of taste is an oral chemical sense in mammals that is involved in the choice of foods. Initial transduction of taste stimuli occurs in taste buds, which are distributed in four discrete fields in the oral cavity. Medications can affect the taste buds and ion channels in taste-bud cell membranes involved in stimulus transduction. The sense of taste gradually declines with aging, with bitter taste most affected. Neural circuits that mediate taste in primates include cranial nerves VII, IX, and X, the solitary nucleus in the brain stem, the ventroposteromedial nucleus of the thalamus, and the insular-opercular cortex. The central taste pathways process taste information about sweet, salty, sour, and bitter stimuli serially and in parallel. Medications associated with "metallic" dysgeusia and taste losses affect the taste system via unknown mechanisms.

Are the tastes of polycose and monosodium glutamate unique?

To study whether Polycose and monosodium L-glutamate (L-MSG) have unique tastes differing from the traditional four basic tastes, chemosensory profiles were established for Polycose, L-MSG and a group of related compounds (sucrose, maltose, monosodium D-glutamate (D-MSG), sodium chloride, calcium chloride). Flavors were assessed using whole-mouth tests in human subjects with nose open or clamped to reduce olfactory input. Polycose (a mixture of glucose-based oligosaccharides) had a flavor consisting of an olfactory component and a maltose-like taste. L-MSG and D-MSG profiles differed from each other, and from NaCl and CaCl2. L-MSG had a lower threshold and a higher frequency of 'other' tastes than the D form. The data do not support a 'polysaccharide' taste, but suggest a chiral receptor site for 'umami' taste.

Nerve fibers sensitive to ionic taste stimuli in chorda tympani of the rat.

Hypotheses about the peripheral basis for the sense of taste in mammals have been based to a considerable degree on the determined sensibilities of the nerve fibers in the chorda tympani of the rat to chemical stimulation of the anterior tongue. Yet, whether neuron types exist in this nerve, the nature of the basic mechanisms of taste reception that are tapped by this nerve and the form in which information about stimulus quality and intensity is transmitted to the central nervous system by this nerve are, at present, unresolved issues. These issues are addressed in the present study, which is a detailed analysis of the responses of rat chorda tympani nerve fibers that are sensitive to ionic stimuli; solutions applied to the anterior tongue included a range of concentrations of four chemical compounds (sucrose, sodium chloride, hydrochloric acid, and quinine hydrochloride) that represent widely different taste qualities to man or rat. Of the 44 nerve fibers sampled, 40 were stimulated most by one of the two ionic stimuli at test concentrations reported to be equally effective: 21 fibers were most responsive to 0.1 M NaCl and named N units; 19 fibers were most responsive to 0.01 M HCl and named H units. Although many N and H units responded to both HCl and NaCl, the distribution of NaCl-HCl response ratios was bimodal, indicating there are two varieties of units sensitive to ionic taste stimuli in the rat chorda tympani. Sucrose (0.5 M) affected 4 of the nerve fibers and was the most effective stimulus for 3 of them; 0.02 M quinine affected 13 of the fibers but 10 of these were H units. H units were less "specifically tuned" than N units; they were more likely to respond to several of the chemicals. Although the absolute sensitivity to NaCl in N units or to HCl in H units varied more than 10-fold, the relative effects of the four stimuli (response profiles) were generally similar for units of a given type. Exceptions occurred when H unit responses to NaCl or quinine were suppressed by prolonged effects of preceding HCl stimulation. The similarity in response profiles is reflected in high and significant correlations between responses to each pair of effective stimuli across either H or N units.(ABSTRACT TRUNCATED AT 400 WORDS)

Taste confusions following gymnemic acid rinse.

The effect of a gymnemic acid (GA) rinse, which simulated a sweet-taste deficit, was measured on human taste perception and identification. Taste ratings showed that GA reduced the intensities of sucrose and aspartame to 14% of pre-rinse levels; over the recovery interval of 30 min, these values increased linearly to 63% of the pre-rinse levels. Repeated presentations of a set of 10 stimuli (five primarily or partly sweet--sucrose, aspartame, and NaCl-sucrose, acid-sucrose and quinine-sucrose mixtures; and five nonsweet--NaCl, KCl, Na glutamate (MSG), quinine HCl and citric acid) for identification following water and GA rinses produced 'taste confusion matrices' (TCMs). Correct identification of the sweet-tasting stimuli was reduced by 23% in presentations closely following the GA rinse, an effect that dissipated with time. Most misidentifications involved sucrose and mixtures containing sucrose. In a second TCM experiment, GA was presented frequently within each session to maintain the sweet taste deficit, which revealed itself as specific confusions. Rinsing with GA impaired discriminability of sweet-nonsweet pairs of stimuli but enhanced discriminability of the aspartame-(NaCl-sucrose) pair. GA had no effect on discriminability of nonsweet stimulus pairs. The results suggest that specific error patterns in the TCM could be used to identify quality-specific taste disorders.

Taste qualities of solutions preferred by hamsters.

Molecules of diverse chemical structure are sweet to humans and several lines of evidence (genetic, physiological, behavioral) suggest that there may be distinct sweet perceptual qualities. To address how many perceptual categories these molecules elicit in hamsters (Mesocricetus auratus), we studied patterns of generalization of conditioned taste aversions for seven sweeteners: 100 mM sucrose, 320 mM maltose, 32 mM D-phenylalanine, 3.2 mM sodium saccharin, 16 mM calcium cyclamate, 10 mM dulcin and 32 mM sodium m-nitrobenzene sulfonate. Each stimulus was preferred versus water in two-bottle intake tests and stimulated the chorda tympani nerve. For each of seven experimental groups the conditional stimulus (CS) was a sweetener and for the control group the CS was water. Apomorphine.HCl was injected i.p. after a CS was sampled and, after recovery, test stimuli (TS) were presented for 1 h daily. The intake (ml) of each TS consumed by experimental animals was compared with mean TS intake by the control group. Learned aversions for 18/21 stimulus pairs cross-generalized, resulting in a single cluster of generalization patterns for the seven stimuli. Cross-generalization failures (maltose-cyclamate, maltose-sucrose, cyclamate-NaNBS) may be the consequence of particular stimulus features (e.g. salience, cation taste), rather than the absence of a 'sucrose-like' quality. The results are consistent with a single hamster perceptual quality for a diverse set of chemical structures that are sweet to humans.

A confusion matrix for the study of taste perception.

Taste stimulus identification was studied in order to more thoroughly examine human taste perception. Ten replicates of an array of 10 taste stimuli--NaCl, KCl, Na glutamate, quinine. HCl, citric acid, sucrose, aspartame, and NaCl-sucrose, acid-sucrose, and quinine-sucrose mixtures--were presented to normal subjects for identification from a list of corresponding stimulus names. Because perceptually similar substances are confused in identification tasks, the result was a taste confusion matrix. Consistency of identification for the 10 stimuli (T10) and for each stimulus pair (T2) was quantified with measures derived from information theory. Forty-two untrained subjects made an average of 57.4% correct identifications. An average T10 of 2.25 of the maximum 3.32 bits and an average T2 of 0.84 of a maximum 1.0 bit of information were transmitted. In a second experiment, 40 trained subjects performed better than 20 untrained subjects. The results suggested that the identification procedure may best be used to assess taste function following 1-2 training replicates. The patterns of taste confusion indicate that the 10 stimuli resemble one another to varying extents, yet each can be considered perceptually unique.

Visualizing taste papillae in vivo with scanning electron microscopy of a high resolution cast.

A method using polyvinylsiloxane (PVS), a high-resolution dental impression material, to obtain negative images of lingual surfaces is described. Epoxy-resin tongue replicas made from these impressions were examined with scanning electron microscopy (SEM). This method has been developed to visualize structural details of the tongue surface of living human beings and laboratory animals. The utility of the method is demonstrated with hamster tongues, which have well-defined fungiform papillae with single taste pores, and human tongues, which have more variable surface structures. Replicas made from PVS impressions of tongues of living hamsters were compared with the same tongues after fixation. The replicas contained much of the detail present in fixed tongues. With SEM, it was possible to identify individual fungiform papillae, which contained depressions with the size and the location of hamster taste pores. Individual papillae could also be recognized in human-tongue replicas, but taste pores could not be identified with certainty. These replicas provide permanent, three-dimensional records of tongue topography that could be used to document changes due to trauma, disease and aging.