Response properties of macaque monkey chorda tympani fibers

Many of the chorda tympani fibers of crab-eating monkeys respond to more than one of the four basic stimuli (NaCl, sucrose, HCl, and quinine hydrochloride) as well as cooling or warming of the tongue. Fibers could be classified into four categories depending on their best sensitivity to any one of the four basic stimuli. Sucrose-best and quinine-best fibers are rather specifically sensitive to sucrose and quinine, respectively, while salt-best and acid-best fibers respond relatively well to HCl and NaCl, respectively. Saccharin, dulcin, and Pb acetate produce a good response in sucrose-best fibers, but quinine- best and salt-best fibers also respond to saccharin. Highly significant positive correlations exist between amounts of responses to sucrose and those to saccharin, dulcin, and Pb acetate, indicating that these substances produce in the monkey a taste quality similar to that produced by sucrose. Compared with chroda tympani fibers of rats, hamsters, and squirrel monkeys, macaque monkey taste fibers are more narrowly tuned to one of the four basic taste stimuli and more highly developed in sensitivity to various sweet-tasting substances. Also LiCl and NaCl are more effective stimuli for gustatory receptors in macaque monkeys than NH4Cl and KCl. This contrasts with a higher sensitivity to KCl and NH4Cl than to NaCl in chorda tympani fibers of squirrel monkeys.     

Sensitivities of single nerve fibers in the hamster chorda tympani to mixtures of taste stimuli

Responses of three groups of neural fibers from the chorda tympani of the hamster to binary mixtures of taste stimuli applied to the tongue were analyzed. The groups displayed different sensitivities to six chemicals at concentrations that had approximately equal effects on the whole nerve. Sucrose-best fibers responded strongly only to sucrose and D-phenylalanine. NaCl-best and HCl-best fibers, responded to four electrolytes: equally to CaCl2 and nearly equally to HCl, but the former responded more to NaCl, and the latter responded more to NH4Cl. The groups of fibers dealt differently with binary mixtures. Sucrose- best fibers responded to a mixture of sucrose and D-phenylalanine as if one of the chemicals had been appropriately increased in concentration, but they responded to a mixture of either one and an electrolyte as if the concentration of sucrose or D-phenylalanine had been reduced. NaCl- best fibers responded to a mixture as if it were a "mixture" of two appropriate concentrations of one chemical, or somewhat less. But, responses of HCl-best fibers to mixtures were greater than that, approaching a sum of responses to components. These results explain effects on the whole nerve, suggest that the sensitivity of a mammalian taste receptor to one chemical can be affected by a second, which may or may not be a stimulus for that receptor, and suggest that some effects of taste mixtures in humans may be the result of peripheral processes.     

Responses of single taste fibers and whole chorda tympani and glossopharyngeal nerve in the domestic pig, Sus scrofa.

Whole nerve, as well as single fiber, responses in the chorda tympani proper (CT) and glossopharyngeal (NG) nerves of 1- to 7-week-old pigs were recorded during taste stimulation. In the CT acids and in the NG bitter compounds gave the largest responses. Both nerves exhibited large responses to monosodium glutamate (MSG), MSG with guanosine 5'-monophosphate (GMP) and MSG with inositine 5'-monophosphate (IMP) as well as to glycine, xylitol, sucrose, fructose and glucose. Alitame, aspartame, betaine, neohesperedin dihydrochalcone (NHDHC), super-aspartame, saccharin and thaumatin elicited no or little response. Hierarchical cluster analysis of 49 CT fibers separated four major clusters. The M cluster, comprising 28.5% of all fibers, is characterized by strong responses to MSG, KCl, LiCl and NaCl. The responses to NaCl and LiCl were unaffected by amiloride. The H cluster (24.5%) includes units responding principally to acids. The Q cluster (18.5%) responds to quinine hydrochloride (QHCl), sucrose octaacetate (SOA) and salts with amiloride. The S cluster (28.5%) exhibits strong responses to xylitol, glycine and the carbohydrates as well as to MSG alone and to MSG with GMP or IMP. In 31 NG fibers, hierarchical cluster analysis revealed four clusters: the M cluster (10%), responding to MSG and MSG with GMP or IMP; the H cluster (13%), responding to acids; the Q cluster (29%), responding strongly to QHCl, SOA and tilmicosinR; and the S cluster (48%), responding best to xylitol, carbohydrates and glycine but also to the umami compounds. Multidimensional scaling analysis across fiber responses to all stimuli showed the best separation between compounds with different taste qualities when information from both nerves was utilized.     

Sugar best single chorda tympani nerve fiber responses to various sugar stimuli in rat and hamster

1. Sugar best single chorda tympani nerve fiber of rat and hamster were tested with six sugars. 2. Fibers were selected for this experiment, only if they responded to 1.0 M sucrose or 1.0 M maltose and they responded poorly to 0.1 M NaCl. 3. In rat, some single fibers gave larger responses to maltose than to sucrose, while in hamster nearly all nerve fibers responded best to sucrose. 4. The order of effectiveness of sugars was maltose greater than fructose greater than or equal to lactose greater than sucrose greater than glucose greater than galactose in rat and sucrose greater than fructose greater than or equal to glucose greater than or equal to galactose greater than maltose greater than lactose in hamster.     

The organization of taste sensibilities in hamster chorda tympani nerve fibers

Electrophysiological measurements of nerve impulse frequencies were used to explore the organization of taste sensibilities in single fibers of the hamster chorda tympani nerve. Moderately intense taste solutions that are either very similar or easily discriminated were applied to the anterior lingual surface. 40 response profiles or 13 stimulus activation patterns were considered variables and examined with multivariate statistical techniques. Three kinds of response profiles were seen in fibers that varied in their overall sensitivity to taste solutions. One profile (S) showed selectivity for sweeteners, a second (N) showed selectivity for sodium salts, and a third (H) showed sensitivity to salts, acids, and other compounds. Hierarchical cluster analysis indicated that profiles fell into discrete classes. Responses to many pairs of effective stimuli were covariant across profiles within a class, but some acidic stimuli had more idiosyncratic effects. Factor analysis of profiles identified two common factors, accounting for 77% of the variance. A unipolar factor was identified with the N profile, and a bipolar factor was identified with the S profile and its opposite, the H profile. Three stimulus activation patterns were elicited by taste solutions that varied in intensity of effect. Hierarchical cluster analysis indicated that the patterns fell into discrete classes. Factor analysis of patterns identified three common unipolar factors accounting for 82% of the variance. Eight stimuli (MgSO4, NH4Cl, KCl, citric acid, acetic acid, urea, quinine HCl, HCl) selectively activated fibers with H profiles, three stimuli (fructose, Na saccharin, sucrose) selectively activated fibers with S profiles, and two stimuli (NaNO3, NaCl) activated fibers with N profiles more strongly than fibers with H profiles. Stimuli that evoke different patterns taste distinct to hamsters. Stimuli that evoke the same pattern taste more similar. It was concluded that the hundreds of peripheral taste neurons that innervate the anterior tongue play one of three functional roles, providing information about one of three features that are shared by different chemical solutions.     

Effects of isoproterenol treatment on gustatory neural responses in three inbred strains of mice

1. Treatment of a beta-agonist, isoproterenol, for 5 days reduced chorda tympani responses to sucrose by about 40% of the control without affecting responses to other taste stimuli, such as NaCl, HCl and quinine HCl, in balb CrSlc mice whereas such reduction of sucrose responses was not observed in C57BL/6-CrSlc and C3H/HeSlc mice, although in the latter two strains long-lasting off-responses to quinine HCl appeared after the treatment. 2. In BALB mice, the magnitude of reduction of sucrose responses by isoproterenol increased with prolonging the treatment from 1 to 5 days, although it reached almost its maximum level by the 3 days treatment. 3. BALB mice with the removal of the submandibular glands showed slightly greater control responses of the chorda tympani nerve to sucrose than BALB mice with the sham-operation or the removal of the sublingual glands, and showed no significant reduction of sucrose responses by isoproterenol treatment. 4. These results suggest that isoproterenol probably did not act directly on sweetener receptors of taste cell membranes but affect them through the submandibular salivary system.     

Inhibition of hamster chorda tympani neural response by copper chloride

Copper chloride was evaluated as a specific inhibitor of neuralresponses to sweet taste stimuli in the goldern hamster (Mesocricetusauratus). The chorda tympani whole-nerve response to taste stimuliwas recorded before and after the tongue was treated for 30s with 0.01, 0.1 and 1 mM CuCl₂. Sweet stimuli [sucrose, fructose,saccharin (calcium salt), D-phenylalanine], which primarilystimulate chorda tympani S fibers, and non-sweet stimuli (NaCl,NH₄Cl) were used. At 0.01 mM, copper chloride had little effect.At 0.10 mM it partially inhibited responses to sucrose and saccharin,but had little effect on responses to D-Phe, fructose, NaCl,NH₄Cl, or a mixture of sucrose plus L-Phe. L-Phe, which hasthe same chelating properties as D-Phe, is not an S-fiber stimulusand likely reduced sucrose inhibiton by chelating the cupricion.Analysis of concentration–response functions revealedthat 0.1 mM copper chloride inhibited the neural response tolow concentrations of sucrose by about 25%, but did not significantlyinhibit high concentrations of surcrose, suggesting competitiveinhibition. In contrast, 0.1 mM CuCl₂ reduced saccharin responsesby 25% throughtout the effective range, suggesting non-competitiveinhibition. Occupation of a saccharide receptor site by coppermay interfere with dimer but not monomer reception and distortthe saccharin receptor site. At 1 mM, CuCl₂ non-competitivelyinhibited responses to sucrose, fructose, saccharin and thenon-sweet NaCl (an N-fiber stimulus), but not NH₄Cl (an H-fiberstimulus). The mechanisms of copper chloride inhibition aredifficult to establish because its effects are weak at concentrationswhere they are specific.     

Changes in the activity of the taste receptor apparatus and the preference for a sodium chloride solution in newborn rats receiving capsaicin]

Taste receptor organ activity and preference of sodium chloride solution in rats with deficit of substance P (SP) were studied. Total impulse activity of chorda tympani nerve of 7-8 week old rats was recorded under nembutal anesthesia. The taste responses to four solutions (sucrose, quinine sulfate, sodium chloride and citric acid) were decreased in rats injected with capsaicin in comparison with rats injected with vehicle. The rats injected with capsaicin preferred water to sodium chloride (two-bottle technique). On the contrary the rats injected with capsaicin preferred the salt solution. These data together with previous studies show the important role of peptide SP in taste receptor activity and "salt appetite".     

Peripheral neural basis for behavioural discrimination between glutamate and the four basic taste substances in mice

1. Single chorda tympani fibres sensitive to monosodium L-glutamate (MSG), elicit a unique taste in humans and gave a greater response to NaCl and/or sucrose than to MSG whereas several MSG-sensitive glossopharyngeal fibres responded only slightly if at all to NaCl and sucrose. 2. The across-fibre correlations showed that MSG and NaCl produced similar response patterns in the chorda tympani fibres but different response patterns in the glossopharyngeal fibres. 3. These results suggest that taste information of glossopharyngeal fibres plays a relatively more important role in the qualitative discrimination between MSG and the four basic taste substances than that of chorda tympani fibres.     

Taste responses of the gerbil IXth nerve

Summated taste responses to 12 taste solutions were recordedfrom the IXth (glossopharyngeal) nerve of 38 Mongolian gerbils(Meriones unguiculatus). 0.3 M NH₄Cl was the most effectivestimulant. The relative magnitude of the peak summated responsewas a positively accelerated function of log molar concentration.Absolute thresholds were determined for three chemicals: 0.002M NaCl, 0.0003 M HCl, and 0.002 M sucrose. The relative magnitudesof the responses to quinine, NH₄Cl, and KCl were greater forthe IXth nerve than for the chorda tympani nerve, whereas NaClwas more effective for the chorda tympani. A similar patternis seen in the rat. Acetic and citric acid may bind to commonreceptor sites. NH₄Cl, KCl, and HCl may also have receptor sitesin common.     

ON THE GUSTATORY EFFECTS OF MONELLIN AND THAUMATIN IN DOG, HAMSTER, PIG AND RABBIT

The electrical activity in the chorda tympani proper nerve ofdog, hamster, pig and rabbit was recorded during stimulationof the tongue with the sweet proteins, monellin and thaumatin,and stimuli representing the four taste qualities. It was observedthat these proteins, which to man taste extremely sweet andin the monkey elicit a significant neural response, caused,except for monellin in the dog, no significant change in theneural activity. On the basis of these results it is suggestedthat different types of ‘sweet’ receptor sites existin mammals.     

Stimulation of bitterness by capsaicin and menthol: differences between lingual areas innervated by the glossopharyngeal and chorda tympani nerves

Capsaicin is viewed as a purely chemesthetic stimulus that selectively stimulates the somatosensory system. Here we show that when applied to small areas of the tongue, capsaicin can produce a bitter taste as well as sensory irritation. In experiment 1, individuals were screened for the ability to perceive bitterness from capsaicin on the circumvallate papillae. Fifteen of 25 subjects who reported at least weak bitterness rated the intensity of taste, irritation and coolness produced by 100-320 microM capsaicin and 100-320 mM menthol applied via cotton swabs to the tip (fungiform region), the posterior edge (foliate region), and the dorsal posterior surface (circumvallate region) of the tongue. Sucrose, citric acid, sodium chloride and quinine hydrochloride were applied to the same areas to assess tastes responsiveness. On average, capsaicin and menthol produced "moderate" bitterness (and no other significant taste qualities) in the circumvallate region, and weaker bitterness on the side and tip of the tongue. Sensory irritation from capsaicin was rated significantly higher at the tongue tip, whereas menthol coolness was rated higher in the circumvallate region. In experiment 2 we applied sucrose and quinine hydrochloride together with capsaicin to investigate the effects other taste stimuli might have on capsaicin's reported bitterness. As expected, adding quinine produced stronger bitterness in the circumvallate and fungiform regions, and adding sucrose significantly reduced the bitterness of capsaicin in the circumvallate region. Overall, the results suggest that capsaicin and menthol are capable of stimulating a subset of taste neurons that respond to bitter substances, perhaps via receptor-gated ion channels like those recently found in capsaicin- and menthol-sensitive trigeminal ganglion neurons, and that the glossopharyngeal nerve may contain more such neurons than the chorda tympani nerve. That some people fail to perceive bitterness from capsaicin further implies that the incidence of capsaicin-sensitive taste neurons varies across people as well as between gustatory nerves.     

A study on the gustatory effects of tetrodotoxin in rat (author's transl)]

Effects of tetrodotoxin (TTX) on neural responses of the chorda tympani to four basic taste stimuli were investigated electrophysiologically in rats. When the TTX (10 mg/ml) was applied directly to the tongue surface for 3 minutes, magnitude of the integrated responses of the chorda tympani was diminished to about 60% of that of the control response. This diminution of response was recovered within 30 minutes by degrees and the effect of the TTX was antagonized by guanylate. This result gives a suggestion that guanidyl group in the TTX may play an important role for the inhibitory actions to the responses of the chorda tympani. On the other hand, when the TTX (0.25 mg/100 g b. wt.) was applied intravenously, magnitude of the responses of the chorda tympani to four basic taste stimuli decreased gradually to 20 approximately 30% of that of the control responses within 60 minutes and did not recover more than 10 hours. This is assumed due to the blocking of the sodium pump of nerve fibers in the chorda tympani by the TTX.     

Sodium deprivation alters neural responses to gustatory stimuli

The effects of sodium deprivation for 10 d, a period sufficient to induce sodium appetite, on gustatory nerve discharges in rats were determined. Chorda tympani responses to concentration series of sodium chloride, sucrose, hydrochloric acid, and quinine hydrochloride were recorded and analyzed without the experimenter knowing the animal's deprivation condition. After deprivation, both whole nerve and single nerve fiber responses to sodium chloride were smaller; NaCl-best fibers, those more responsive to sodium chloride than to sucrose, hydrochloric acid, or quinine, were most affected. Thresholds had not changed; however, slopes of the stimulus-response functions for sodium chloride were lowered. Comparable changes in responses to the other stimuli did not occur. These results were discussed with respect to a possible relationship between changes in sodium chloride responsivity and changes in sodium intake, differences between methods of inducing sodium appetite, coding of taste quality and intensity, and mechanisms which might effect the responsivity change.     

The sweet taste quality is linked to a cluster of taste fibers in primates: lactisole diminishes preference and responses to sweet in S fibers (sweet best) chorda tympani fibers of M. fascicularis monkey

Background

Psychophysically, sweet and bitter have long been considered separate taste qualities, evident already to the newborn human. The identification of different receptors for sweet and bitter located on separate cells of the taste buds substantiated this separation. However, this finding leads to the next question: is bitter and sweet also kept separated in the next link from the taste buds, the fibers of the taste nerves? Previous studies in non-human primates, P. troglodytes, C. aethiops, M. mulatta, M. fascicularis and C. jacchus, suggest that the sweet and bitter taste qualities are linked to specific groups of fibers called S and Q fibers. In this study we apply a new sweet taste modifier, lactisole, commercially available as a suppressor of the sweetness of sugars on the human tongue, to test our hypothesis that sweet taste is conveyed in S fibers.

Results

We first ascertained that lactisole exerted similar suppression of sweetness in M. fascicularis, as reported in humans, by recording their preference of sweeteners and non- sweeteners with and without lactisole in two-bottle tests. The addition of lactisole significantly diminished the preference for all sweeteners but had no effect on the intake of non-sweet compounds or the intake of water. We then recorded the response to the same taste stimuli in 40 single chorda tympani nerve fibers. Comparison between single fiber nerve responses to stimuli with and without lactisole showed that lactisole only suppressed the responses to sweeteners in S fibers. It had no effect on the responses to any other stimuli in all other taste fibers.

Conclusion

In M. fascicularis, lactisole diminishes the attractiveness of compounds, which taste sweet to humans. This behavior is linked to activity of fibers in the S-cluster. Assuming that lactisole blocks the T1R3 monomer of the sweet taste receptor T1R2/R3, these results present further support for the hypothesis that S fibers convey taste from T1R2/R3 receptors, while the impulse activity in non-S fibers originates from other kinds of receptors. The absence of the effect of lactisole on the faint responses in some S fibers to other stimuli as well as the responses to sweet and non-sweet stimuli in non-S fibers suggest that these responses originate from other taste receptors.     

Reduction of saltiness and bitterness after a chlorhexidine rinse

Chronic rinsing with chlorhexidine, an oral-antiseptic, has been shown to decrease the saltiness of NaCl and the bitterness of quinine. The effect of acute chlorhexidine on taste has not been investigated. The purpose of the present study was to examine the effect of acute chlorhexidine rinses on taste intensity and quality of 11 stimuli representing sweet, salt, sour, bitter and savory. All stimuli were first matched for overall intensity so the effects of chlorhexidine would be directly comparable across compounds. As a control treatment, the bitter taste of chlorhexidine digluconate (0.12%) was matched in intensity to quinine HCl, which was found to cross-adapt the bitterness of chlorhexidine. Subjects participated in four experimental conditions: a pre-test, a quinine treatment, a chlorhexidine treatment, and a post-test condition, while rating total taste intensity and taste qualities in separate test sessions. Relative to the quinine treatment, chlorhexidine was found to decrease the salty taste of NaCl, KCl and NH4Cl, and not to significantly affect the tastes of sucrose, monosodium glutamate (MSG), citric acid, HCl and the taste of water. The bitter taste of urea, sucrose octa-acetate and quinine were suppressed after chlorhexidine rinses relative to water rinses, but were only marginally suppressed relative to quinine rinses. Potential mechanisms are discussed.     

Effects of binary taste stimuli on the neural activity of the hamster chorda tympani

Binary mixtures of taste stimuli were applied to the tongue of the hamster and the reaction of the whole corda tympani was recorded. Some of the chemicals that were paired in mixtures (HCl, NH4Cl, NaCl, CaCl2, sucrose, and D-phenylalanine) have similar tastes to human and/or hamster, and/or common stimulatory effects on individual fibers of the hamster chorda tympani; other pairs of these chemicals have dissimilar tastes and/or distinct neural stimulatory effects. The molarity of each chemical with approximately the same effect on the activity of the nerve as 0.01 M NaCl was selected, and an established relation between stimulus concentration and response allowed estimation of the effect of a "mixture" of two concentrations of one chemical. Each mixture elicited a response that was smaller than the sum of the responses to its components. However, responses to some mixtures approached this sum, and responses to other mixtures closely approached the response to a "mixture" of two concentrations of one chemical. Responses of the former variety were generated by mixtures of an electrolyte and a nonelectrolyte and the latter by mixtures of two electrolytes or two nonelectrolytes. But, beyond the distinction between electrolytes and nonelectrolytes, the whole-nerve response to a mixture could not be predicted from the known neural or psychophysical effects of its components.     

Specific changes in the sodium chloride intake and activity of the taste receptor apparatus of rats administered the peptide litorin and its albumin conjugate

The role of bombesin-like peptide litorin in control of salt consumption was studied in rats. The influence of exogenous injection and binding of the endogenous litorin in the organism on the consumption of sodium chloride and sucrose solutions was analyzed in deprived rats in the process of 15-min. testing. It was found that intraperitoneal injection of 10(-6) - 10(-5) M of litorin led to an increase, and rats immunization by peptide conjugate with ox serum albumin--to a decrease of the consumption of salt solution, without changing the consumption of sucrose solution. Titres of antibodies to litorin in the plasma of rats immunized with the conjugate were higher than in the control. Intraperitoneal, subcutaneous or intranasal injections of 10(-5) M of litorin led to selective increase of gustatory responses (recorded from the chorda tympani) to tongue stimulation by salt and acid solutions not influencing the responses to quinine and sucrose in anesthetized rats. The study shows, that the peptide litorin selectively participates in the control of sodium chloride consumption. In the process of such control the increase of taste apparatus sensitivity to the sodium chloride is probably involved.     

Residual chemoresponsiveness to acids in the superior laryngeal nerve in "taste-blind" (P2X2/P2X3 double-KO) mice

Mice lacking both the P2X2 and the P2X3 purinergic receptors (P2X-dblKO) exhibit loss of responses to all taste qualities in the taste nerves innervating the tongue. Similarly, these mice exhibit a near total loss of taste-related behaviors in brief access tests except for a near-normal avoidance of acidic stimuli. This persistent avoidance of acids despite the loss of gustatory neural responses to sour was postulated to be due to continued responsiveness of the superior laryngeal (SL) nerve. However, chemoresponses of the larynx are attributable both to taste buds and to free nerve endings. In order to test whether the SL nerve of P2X-dblKO mice remains responsive to acids but not to other tastants, we recorded responses from the SL nerve in wild-type (WT) and P2X-dblKO mice. WT mice showed substantial SL responses to monosodium glutamate, sucrose, urea, and denatonium-all of which were essentially absent in P2X-dblKO animals. In contrast, the SL nerve of P2X-dblKO mice exhibited near-normal responses to citric acid (50 mM) although responsiveness of both the chorda tympani and the glossopharyngeal nerves to this stimulus were absent or greatly reduced. These results are consistent with the hypothesis that the residual avoidance of acidic solutions by P2X-dblKO mice may be attributable to the direct chemosensitivity of nerve fibers innervating the laryngeal epithelium and not to taste.     

Sour taste responses in mice lacking PKD channels

Background

The polycystic kidney disease-like ion channel PKD2L1 and its associated partner PKD1L3 are potential candidates for sour taste receptors. PKD2L1 is expressed in type III taste cells that respond to sour stimuli and genetic elimination of cells expressing PKD2L1 substantially reduces chorda tympani nerve responses to sour taste stimuli. However, the contribution of PKD2L1 and PKD1L3 to sour taste responses remains unclear.

Methodology/Principal Findings

We made mice lacking PKD2L1 and/or PKD1L3 gene and investigated whole nerve responses to taste stimuli in the chorda tympani or the glossopharyngeal nerve and taste responses in type III taste cells. In mice lacking PKD2L1 gene, chorda tympani nerve responses to sour, but not sweet, salty, bitter, and umami tastants were reduced by 25–45% compared with those in wild type mice. In contrast, chorda tympani nerve responses in PKD1L3 knock-out mice and glossopharyngeal nerve responses in single- and double-knock-out mice were similar to those in wild type mice. Sour taste responses of type III fungiform taste cells (GAD67-expressing taste cells) were also reduced by 25–45% by elimination of PKD2L1.

Conclusions/Significance

These findings suggest that PKD2L1 partly contributes to sour taste responses in mice and that receptors other than PKDs would be involved in sour detection.