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Department of Animal Health and Biomedical Sciences, University of Wisconsin, Madison, Wisconsin 53706
Submitted 9 December 2003; accepted in final form 1 April 2004
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ABSTRACT |
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 TOP ABSTRACT INTRODUCTIONMETHODSRESULTSDISCUSSIONGRANTSACKNOWLEDGMENTSREFERENCES |
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INTRODUCTION |
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TOPABSTRACTINTRODUCTIONMETHODSRESULTSDISCUSSIONGRANTSACKNOWLEDGMENTSREFERENCES |
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; Zuhlke and Weinbauer 2003). It is phylogenetically less related to humans than Old World monkeys, such as macaques, but in spite of that is often used as an animal model of humans. We have explored its sense of taste in a few previous studies (Danilova et al. 1998a, 2002; Hellekant et al. 1981). In the latest study, we recorded the responses of single taste fibers in the two major nerves supplying the tongue, the chorda tympani (CT) and glossopharyngeal nerve (NG). We used 40 compounds representing the four human taste qualities, sweet, bitter, sour, and salty. In both the CT and NG, our analysis identified three groups of taste fibers: the S fibers, responding predominantly to sweeteners, the Q fibers responding predominantly to bitter compounds, and the H fibers responding predominantly to sour compounds.
Our studies in primates as well as in non-primates suggest that acceptance or rejection of a compound is influenced by how much it stimulates S or Q taste fibers (Brouwer et al. 1983; Danilova et al. 1998b; Hellekant et al. 1997a, 1998). It seems that this theory is presently receiving support by the finding of separate sets of receptors responding to either compounds, which we human call sweet and generally like or bitter and generally reject (Nelson et al. 2001; Zhang et al. 2003; Zhao et al. 2003). These receptors, identified in mice and humans, belong to two families of receptors T1Rs and T2Rs and are localized in different cells of the taste buds. Therefore already separated information on the taste quality has the potential to be transmitted through different taste fibers.
Here we hypothesize that if sweet and bitter tastes are conveyed in different sets of nerve fibers, then we should be able to relate a species intake of a compound to the distribution of activity in its S and Q fibers. We demonstrated this in hamster (Danilova et al. 1998b). We also tested this hypothesis in a recent study using S fiber responses as a measure of sweetness (Jin et al. 2003). We found a high correlation (0.76) between the S fiber responses to 28 sweeteners in rhesus monkeys and psychophysical results in humans for the same array of compounds. Here we tested if activity in S fibers was related to intake and activity in Q fibers to rejection using two-bottle preference (TBP) and conditioned taste aversion (CTA) techniques. Although it is implicit that consumption is also influenced by many other factors, including postingestive factors, learning experience, and homeostasis of an animal, we concentrated on the role of S and Q fibers in this study.
A short summary of the results with the TBP method has been published earlier (Danilova et al. 1998b).
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METHODS |
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TOPABSTRACTINTRODUCTIONMETHODSRESULTSDISCUSSIONGRANTSACKNOWLEDGMENTSREFERENCES |
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TBP experiments
A total of 21 adult marmosets of both sexes were used as subjects. Three animals were tested as individuals and 18 as pairs. No distinction between the consumption of the two in a pair was attempted. Thus the consumption of each pair was considered as one measurement. Table 1 shows the number of cages tested and presentation time for each stimulus.
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The preference ratio was calculated as the amount of a test solution consumed divided by the total amount of liquid consumed. Thus equal consumption from both bottles resulted in a preference ratio of 0.5; consumption from only the stimulus bottle resulted in a preference ratio of 1. The preference ratios were averaged for 2 days. The results were first assessed using ANOVA. Then a two-tailed t-test was used to compare mean preference ratios with 0.5. A P < 0.01 value was considered as a significant level.
Conditioned taste aversion experiments
Twenty-four naive adult marmosets of both sexes, housed as pairs, were used as subjects. They were separated only during the conditioning (
1 h) and the tests (2–10 h). The animals were first trained to drink water from a lickometer, a device that measures consumption as a number of licks from 16 different bottles mounted in a carousel. Each lick broke an infrared beam positioned between the animal and the bottle in use and triggered one count by the computer. The first lick started a timer that limited the presentation to 30 s. On completion of training the animals drank only from the lickometer.
The marmosets were then offered a 0.3 M sucrose solution (conditioning stimulus). After consumption of the sucrose, 3 ml 0.3 M LiCl (unconditioning stimulus) was injected itramuscularly within 30 min. After a 1-day rest, we tested if the animals were successfully conditioned. If the consumption of sucrose was suppressed to a level <10% of water consumption, the animals were considered conditioned. If their consumption of sucrose was not suppressed, LiCl was administered again. No animal needed more than two injections. The control animals underwent the same routine but with NaCl injections.
We obtained data from 13 control and 11 conditioned animals. In each series, the marmosets were tested with three cycles of presentations of 16 taste stimuli, including distilled water and sucrose. The presentation order within cycles was randomized. We ran four series of experiments: two different series with a single concentration of 30 sweeteners, one concentration series with 3 sweeteners and one series of acids. Because multiple presentations of sucrose and other sweeteners attenuate the reflex, each conditioned animal participated only in two series, whereas most of the control animals participated in every series.
Because the level of drinking differed between animals, the consumption of sweeteners was normalized to a "standard." For each animal, we considered the average number of licks of water during three cycles as the standard and assigned it the value 100%. Then for each marmoset, consumption of all stimuli was expressed in percentage of this standard. The data were then averaged for the control and conditioned animals.
Using a t-test for independent samples, we analyzed the difference in consumption by control and conditioned animals. A P < 0.01 value was considered as a significant difference in the statistical analysis.
Lickometer tests with salts
Five naive marmosets were tested in this series. The lickometer and the training procedure were the same as in the previous CTA series. The marmosets were offered six concentrations of NaCl, three of LiCl, and four of KCl. As controls, 20 mM citric acid, 0.1 M sucrose, 2.5 mM QHCl, and water were included. Each stimulus was presented three times in random order. The consumption of stimuli was also expressed as percent of water consumption.
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RESULTS |
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Figure 1 presents the result of the TBP tests with the compounds arranged in an order of increasing preference. The stimuli can be divided into three groups. The first group was composed of compounds whose preference ratios were significantly lower than 0.5, which means that they were rejected. These included, as expected, five bitter compounds but also two compounds generally considered as sweeteners, D-phenylalanine and stevioside.
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The compounds of the third group included the 20 sweeteners the preference ratios of which were significantly higher than 0.5, and therefore these compounds were preferred over water.
Results of CTA tests
Figure 2 shows the consumption of sweeteners by 10 control (
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) marmosets. It shows the number of licks for each compound expressed in percentage of number of licks for plain water. The sweeteners are arranged in order of increasing consumption by the control group. The level of consumption of sweeteners in the control group can be considered as a measure of liking. The vertical lines on the Fig. 2 separate three groups of compounds that the control animals consumed significantly less than water and therefore did not like, consumed at the same level as water, and consumed significantly higher than the 100% level of water consumption and therefore preferred. The orders of preferences observed in TBP and CTA (control group) were highly correlated. The Spearman correlation coefficient was 0.78 (P < 0.01).
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To see if the concentrations of saccharin, aspartame, and ampame were too low for a preference, we tested several higher concentrations than in Fig. 2. Then the control group consumed these compounds significantly less than water, indicating a nonsweet or aversive taste. In the conditioned group, there was no significant change in consumption (data not shown).
Results of CTA experiments with acid series
Figure 3 shows the results of the experiments with acids and acid/sucrose mixtures in nine control and two conditioned marmosets. The control and conditioned animals gave similar results with acids. At low concentrations, acids were neither preferred nor rejected, but at high concentrations, acids were significantly rejected.
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In the conditioned animals, the consumption of all acid/sucrose mixtures was as low as consumption of acids alone. This indicated that marmosets distinguished the taste of sucrose in the mixtures and avoided it.
Results of lickometer tests with salts
Figure 4 shows relationships between concentration and level of consumption for three different salts, NaCl, LiCl, and KCl. The results demonstrated that marmosets tasted all three salts and their consumption significantly decreased with an increase of concentration. The response-concentration curves were also calculated and the data fit a logarithmic curve quite well. The equation for each salt is given in top right part of the graphs. The curve fit correlation coefficients for the three graphs in Fig. 4 are 0.86, 0.92, and 0.93, respectively.
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DISCUSSION |
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, 2002; Hellekant et al. 1981). In the following, we compare the behavioral findings with the results we previously recorded in single taste fibers. By combining these methods, we can estimate quite well how a compound may taste to marmosets. We applied the TBP method in both short (15 min)- and long-term (24 h) tests. Because the behavioral reaction might be influenced by postingestive effects, the data on preference for as many of the sweeteners as possible were obtained in short-term experiments. However, if the compound was not preferred in the 15-min test, it could indicate that either the monkey did not distinguish the taste of the compound (it tasted like water) or the monkey was not attracted to its taste (it was either aversive or neither attractive nor aversive). To force the animal to make a choice, we left the bottles for 24 h. The results were divided into two alternatives: either the animals rejected the compound (it had aversive taste) or they consumed the compound as much as water (it tasted like water or was neither attractive nor aversive). We also used the level of consumption by the CTA control group to add information to our short-term TBP data. In the CTA tests, we made the assumption that if the taste of sucrose is generalized to the compound in question, then it has a sucrose-like taste component.
Table 2 summarizes the results of the electrophysiological, TBP, and CTA experiments. The first column shows the result of our earlier electrophysiological experiments with the same compounds and concentrations as used here (Danilova et al. 2002). We discuss the compounds according to the types of fibers they stimulated or did not stimulate.
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Previously we found that seven sweeteners, ASME, brazzein, CAMPA, cyclamate, DMGA, monellin, and NHDHC, did not elicit statistically significant responses in both taste nerves. Here the marmosets showed neither preference nor rejection of these compounds in TPB tests and the consumption of ASME, CAMPA, cyclamate and NHDHC by the control as well as the conditioned animals did not differ from their consumption of water in the CTA tests (brazzein, DMGA, and monellin were not tested in CTA experiments because of lack of compounds). Our TPB results corroborate earlier behavioral experiments in marmosets, which showed no preference for several of the sweeteners used here including ASME, aspartame, CAMPA, cyclamate, and monellin (Glaser et al. 1978, 1995, 1996; Nofre et al. 1996). Taken together the preceding suggests that these compounds in concentrations used here have no taste to marmosets.
This conclusion is interesting because all these seven compounds are sweet to humans. Furthermore, in the Old World primates (rhesus monkeys and chimpanzees) brazzein, cyclamate, monellin, and NHDHC stimulated S fibers and were preferred in behavioral experiments (Hellekant 1997a,1997b).
Aspartame has to be considered separately. It is commonly used as a sweetener in human consumption. In the rhesus monkey and chimpanzee, 5 mM aspartame stimulated S fibers very effectively and was preferred. In the marmoset, although the average response of 11 S and 15 Q fibers to 5 mM aspartame did not meet the criterion for a response, some fibers (6 S and 6 Q) responded. The finding that some S and Q fibers responded to aspartame suggests a complex taste where its sucrose-like taste is counterbalanced by an aversive taste. The small response of the S fibers suggests that the sensitivity of the New World marmoset's sweet receptors to aspartame is much lower than that of Old World primates.
It is interesting that CAMPA and DMGA (which did not activate marmoset's taste fibers and were not preferred) are sweet to humans and in hamster stimulate S fibers and are preferred (Danilova et al. 1998b). Similarly, cyclamate, which gave neither electrophysiological nor behavioral responses in marmosets, is sweet to humans and Old World monkeys and has an attractive taste to mice (Bachmanov et al. 2001). Another example of species differences in taste relates to L-proline. It is bitter-sweet to humans and not preferred by marmosets, but preferred by some mouse strains (Bachmanov et al. 2001; Haefeli et al. 1998; Schiffman et al. 1979). These examples show that the evolution of the sense of taste may follow paths, which are not always related to the phylogeny.
Compounds that stimulated only Q fibers
We have earlier demonstrated in Old World primates that compounds bitter to humans stimulate Q fibers and are rejected in behavioral experiments. We suggested that Q fibers code for aversive taste quality and contribute to rejection (Hellekant et al. 1997a,b). Here in marmosets, all the compounds that stimulated only the Q fibers were also rejected in the TPB tests. This suggests that Q fibers provide hedonically negative information in New World monkeys too.
Compounds that stimulated only S fibers
Of 15 compounds that stimulated only S fibers, 14 were preferred in TBP tests and by the CTA controls. This corroborates earlier findings in marmosets (Glaser et al. 1995; Haefeli and Glaser 1984; Haefeli et al. 1998; Nofre et al. 1996) and observations in other species, including chimpanzee, hamster, pig, and rhesus (Hellekant et al. 1997a,b; Danilova et al. 1998b, 1999). Furthermore these stimuli were avoided by the conditioned animals in the CTA tests, demonstrating that these compounds share taste characteristics with sucrose. Taken together the electrophysiological and behavioral results support the hypothesis that activity in the S fibers codes for a taste quality that is intrinsically attractive.
However, if the attractive taste quality of the conditioned stimulus is paired with the negative unconditioned stimulus (LiCl), the same information from the S fibers is processed by the CNS as a cue for rejection. Another example of the plasticity of the CNS in utilization of the peripheral taste input is increased acceptance of bitter taste after "flavor-nutrient conditioning". Thus after pairing the bitter compound sucrose octaacetate (SOA) with intragastric glucose infusion (positive unconditioned stimulus), the rats demonstrated acceptance and even preference of SOA over a stimulus that was paired with intragastric water infusion (Perez et al. 1998). Although the Q fibers activity was unchanged and signaled the aversive taste of SOA, other nontaste factors played a role in the decision-making.
CAM was the only compound in the group that was not preferred. It is possible that the concentration of CAM was too low to produce a significant preference. However, the input from the S fibers was revealed in the CTA tests because the consumption of CAM was suppressed in the conditioned animals.
Compounds that stimulated S, Q, and H fibers
This group comprised compounds of different taste qualities: acids, acid/sucrose mixtures, and some sweeteners.
Acids.
Both the control and conditioned animals demonstrated stronger aversion with increased acid concentration. In the electrophysiological experiments with acids, the H and Q fibers responded with activity sustained during stimulation and 2–3 s after the end of stimulation (Danilova et al. 2002). Many S fibers showed small transient activity at the beginning of stimulation and then an OFF response during rinsing after stimulation. We think that although there was some response in the S fibers, it was insufficient to cause intake and balance the effect of Q fibers.
Acid/sucrose mixtures. Reactions to acid/sucrose mixtures depended on concentrations used. The Q fiber activity induced aversion and the S fiber activity consumption. Increasing sucrose concentration in the mixtures increases S fiber activity (signaling an intrinsically attractive taste) which then changes the behavior from aversion to preference. In contrast, the conditioned animals avoided the mixtures because the S fibers signaled the taste quality that they learned to avoid. As mentioned in the preceding text, the conditioning occurs in the CNS. The peripheral taste fiber activity remains the same whether the animal is conditioned or not, but how CNS utilizes the activity is changed with conditioning.
Sweeteners.
Ampame, acesulfame-K, NC00174, NC00351, D-phenylalanine, saccharin, stevioside, and xylitol are all sweet to humans but with an additional bitter taste component (Schiffman et al. 1995; unpublished observations). As shown in Table 2 they elicited various reactions in the TBP and CTA tests. We suggest that the balance between the Q and S fiber activity determined the intake of these compounds.
In some cases S fibers exert stronger influence than Q fibers: acesulfame-K, NC00174, and xylitol were preferred and NC00351 was not rejected. The input from the S fibers was revealed by the fact that the intake of these four sweeteners was suppressed in the conditioned animals. However, it is likely that these stimuli also have another non-attractive taste component, because as mentioned they also stimulated Q and in some cases H fibers. The Q fiber input can explain why the control animals in the CTA tests consumed acesulfame-K and NC00351 just as much as water, in spite of the fact that these compounds stimulated S fibers.
In other cases the behavioral results indicated that the Q fiber component exerted stronger influence: ampame, D-phenylalanine and stevioside were rejected in the TBP tests and consumed less than water by the control animals in the CTA test. Similar result with ampame has been reported in marmosets (Glaser et al. 1996). Indeed, the nerve responses to these three compounds showed a large Q fiber component. The influence of the S fibers is difficult to estimate because of a low level of consumption of these stimuli by the control animals in the CTA tests.
Of course there are limitations with regard to this. These limitations might include the impact of other fiber types, or the internal status (hunger, thirst, etc.).
Relationship between behavioral and electrophysiological results
Based on the preceding results and data from our previous studies, especially in primates, we suggest that the S fiber input gives a hedonically positive effect and the Q fibers' to a negative effect. These inputs are then processed and combined in CNS with other factors, such as satiety, experiences, homeostasis, etc. It is implicit that this peripheral input is only one of the factors that influence intake.
Provided that our model is valid, one should be able to predict the intake of a compound in naïve animals using electrophysiological recordings. As a measure of intake we used the preference ratios in the TBP tests here and as a measure of the neuronal activity we suggested to use Net responses from the S and Q fibers in the CT and NG: Net response = (SCT + SNG) – (QCT + QNG). The S and Q fibers' responses to all bitter or/and sweet compounds used here were taken from our previous study (Danilova et al. 2002).
We found a strong linear relationship between the net response and the preference ratio. The Pearson correlation coefficient for these two parameters was 0.85 (P < 0.01). Thus the analysis generally supports our hypothesis that intake reflects balance between S and Q fiber inputs in which S fibers serve as a hedonically positive and Q fibers as a hedonically negative input.
Responses to salts
In many species, fibers responding predominantly to salts, N fibers, have been described and a number of studies suggest that these fibers code for salty taste. This conclusion is supported by data in rats in which treatment with the sodium channel blocker, amiloride, abolished the N-fiber activity and disrupted the discrimination of salt from other taste qualities (Scott and Giza 1990).
As shown in Fig. 4 the intake of NaCl, LiCl, and KCl changed with concentration. This shows that marmosets can taste these salts. On the other hand, we have earlier identified only one N fiber in the CT and none in the NG. This undercuts the idea that salty taste is coded by N fibers in this species (Danilova et al. 2002). However, we recorded in 35% of the CT fibers that these salts first inhibited the activity and then gave an OFF response. This suggests that the temporal pattern may also be used for the coding of salty taste in marmosets. The possibility of a temporal pattern being used to discriminate qualities has been suggested based on data from rat nucleus tractus solitarius (Di Lorenzo and Victor 2003).
Other mechanisms may be at play in taste receptor cells (TRC) and add gustatory information to the Q and S fibers. Considering the fact that there are several cell types in the taste buds and that some of these cells have no evident exposure to the content in the taste pore and several neuropeptides have been found in the taste buds, it is quite likely that some kind of processing of the chemical information occurs in the taste bud (cf. Ewald and Roper 1994; Herness et al. 2002a,b).
Relationship between S/Q fibers and T1R/ T2R receptors
As mentioned in the INTRODUCTION, two families of taste receptors, T1Rs and T2Rs, have been identified. The finding that the human T1R2/R3 responded to compounds sweet to man, whereas the mouse T1R2/T1R3 responded only to compounds attractive to mice suggests that differences in S fiber responsiveness are caused by differences between the receptors (Li et al. 2002; Zhao et al. 2003).
Furthermore, our finding that some sweeteners were not preferred by marmosets, although they are liked by Old World monkeys, suggests dissimilarities between T1Rs also within the primate order. In this context, it should be mentioned that Nofre et al. inferred that species differences in sweet taste are caused by amino acid differences in their sweet receptor (Nofre et al. 1996). This is supported by recent data from Li et al., who found sequence variations in T1R2/T1R3 among 18 primate species and suggested that this could account for differences in the taste response to aspartame (Li et al. 2003).
Electrophysiological data in rhesus monkeys and chimpanzees show a better response to sweet in the CT than the NG, whereas the murine T1R receptors are located mostly on the back of the tongue, which is supplied by the NG nerve (Hoon et al. 1999). Consequently one would expect that the response to sweet in the NG would be better than in the CT. This seemingly contradiction between molecular and electrophysiological data was recently resolved by Liao and Schultz, who demonstrated that T1R genes are expressed selectively in the fungiform papillae of humans and therefore most likely also in other Old World primates (Liao and Schultz 2003). On the other hand, our data in marmosets show little difference between the sweet responses in CT and NG nerves and may indicate that New World primates have a more even distribution of T1Rs on their tongues.
This study, as well as all our previous primate studies, strongly favors the theory of labeled line coding. We would prefer to replace labeled with dedicated. Several studies supporting this theory have recently been published. First, T1Rs and T2Rs never are found in the same TRCs but are located in different TRCs (Nelson et al. 2001). This means that bitter and sweet tastes have to be processed by different TRCs. It does not necessarily mean that sweet and bitter are conveyed in separate nerve fibers because as is well known a taste fiber can innervate more than one TRC. However, there is no reason to assume that the separation between bitter and sweet is not maintained in the taste fibers. Second, in a recent study, Zhang et al. (2003) demonstrated that active transduction in bitter receptor-expressing cells, but not in sweet receptor-expressing cells, is sufficient for aversive responses to bitter. This provides a foundation for our idea that dedicated Q fibers are linked to aversion. Third, Zhao et al. (2003) demonstrated that inactivation of both T1R2 and T1R3 receptors abolished the preference for sweeteners but not aversion to bitter. Fourth, they showed that mice, which previously did not discriminate between water and spiradoline, an opioid ligand, strongly preferred it after the opioid receptor was expressed specifically in T1R2+3-expressing TRCs (Zhao et al. 2003). They also wrote: "together, these results establish that dedicated taste pathways mediate attractive and aversive behavior and strongly support the concept of taste coding using labeled lines," which corroborates our results in a number of studies.
In summary, this and previous studies characterize the gustatory system of a New World monkey, C. jacchus jacchus, with behavioral and electrophysiological techniques. By combining nerve recordings and behavioral techniques, we have presented a further link between S fiber activity and preference and Q fiber activity and rejection. This strengthens our hypothesis that intake is influenced by S and Q fibers, where S fibers serve as a hedonically positive input and Q fibers as a hedonically negative input.
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GRANTS |
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TOPABSTRACTINTRODUCTIONMETHODSRESULTSDISCUSSIONGRANTSACKNOWLEDGMENTSREFERENCES |
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ACKNOWLEDGMENTS |
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TOPABSTRACTINTRODUCTIONMETHODSRESULTSDISCUSSIONGRANTSACKNOWLEDGMENTSREFERENCES |
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FOOTNOTES |
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Address for reprint requests and other correspondence: G. Hellekant, Dept. of Animal Health and Biomedical Sciences, University of Wisconsin-Madison, 1655 Linden Dr., Madison, WI 53706 (E-mail: hellekant{at}svm.vetmed.wisc.edu).
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REFERENCES |
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Brouwer JN, Glaser D, Hard af Segerstad C, Hellekant G, Ninomiya Y, and van der Wel H. The sweetness-inducing effect of miraculin; behavioural and neurophysiological experiments in the rhesus monkey Macaca mulatta. J Physiol 337: 221–240, 1983.
Danilova V, Danilov Y, Roberts T, Tinti, J-M, Nofre, and Hellekant G. The sense of taste in a New World monkey, the common marmoset: recordings from the chorda tympani and glossopharyngeal nerves. J Neurophysiol 88: 579–594, 2002.
Danilova V, Hellekant G, Roberts T, Tinti, J-M, and Nofre C. Behavioral and single chorda tympani taste fiber responses in the common marmoset, Callithrix jacchus jacchus. An. NY Acad Sci 855: 160–164, 1998a.
Danilova V, Hellekant G, Tinti, J-M, and Nofre C. Gustatory responses of the hamster Mesocricetus auratus to various compounds considered sweet by humans. J Neurophysiol 80: 2102–2112, 1998b.
Danilova V, Roberts T, and Hellekant G. Responses of single taste fibers and whole chorda tympani and glossopharyngeal nerve in the domestic pig, Sus scrofa. Chem Senses 24: 301–316, 1999.
Di Lorenzo PM and Victor JD. Taste response variability and temporal coding in the nucleus of the solitary tract of the rat. J Neurophysiol 90: 1418–1431, 2003.
Ewald DA and Roper SD. Bidirectional synaptic transmission in Necturus taste buds. J Neurosci 14: 3791–3804, 1994.[Abstract]
Glaser D, Hellekant G, Brouwer JN, and van der Wel H. The taste responses in primates to the proteins thaumatin and monellin and their phylogenetic implications. Folia Primatol 29: 56–63, 1978.
Glaser D, Tinti GM, and Nofre C. Evolution of the sweetness receptor in primates. I. Why does alitame taste sweet in all Prosimians and Simians and aspartame only in Old World Simians? Chem Senses 20: 573–584, 1995.
Glaser D, Tinti JM, and Nofre C. Gustatory responses of non-human primates to dipeptide derivatives or analogues, sweet in man. Food Chem 56: 313–321, 1996.[CrossRef]
Haefeli RJ and Glaser D. Gustatory threshold values of xylitol in primates. Folia Primatol 43: 181–184, 1984.
Haefeli RJ, Solms J, and Glaser D. Taste responses to amino acids in common marmosets (Callithrix jacchus jacchus, Callitrichidae) a non-human primate in comparison to humans. Öebensm Wiss Technol 31: 371–375, 1998.[CrossRef]
Hellekant G, Danilova V, and Ninomiya Y. Primate sense of taste: behavioral and single chorda tympani and glossopharyngeal nerve fiber recordings in the rhesus monkey, Macaca mulatta. J Neurophysiol 77: 978–993, 1997a.
Hellekant G, Glaser D, Brouwer JN, and van der Wel H. Gustatory responses in three prosimian and two simian primate species (Tupaia glis, Nycticebus coucang, Galago senegalensis, Callithrix jacchus jacchus and Saginus midas niger) to six sweeteners and miraculin and their phylogenetic implications. Chem Senses 6: 165–173, 1981.
Hellekant G, Ninomiya Y, and Danilova V. Taste in chimpanzees II. single chorda tympani fibers. Physiol Behav 61: 829–841, 1997b.[CrossRef][Medline]
Hellekant G, Ninomiya Y, and Danilova V. Taste in chimpanzees III. Labeled line coding in sweet taste. Physiol Behav 65: 191–200, 1998.[CrossRef][Medline]
Herness S, Zhao FL, Kaya N, Lu SG, Shen T, and Sun XD. Adrenergic signalling between rat taste receptor cells. J Physiol 543: 601–614, 2002a.
Herness S, Zhao FL, Lu SG, Kaya N, and Shen T. Expression and physiological actions of cholecystokinin in rat taste receptor cells. J Neurosci 22: 10018–10029, 2002b.
Hoon MA, Adler E, Lindemeier J, Battey JF, Ryba NJ, and Zuker CS. Putative mammalian taste receptors: a class of taste-specific GPCRs with distinct topographic selectivity. Cell 96: 541–551, 1999.[CrossRef][ISI][Medline]
Jin Z, Danilova V, Assadi-Porter FM, Markley JL, and Hellekant G. Monkey electrophysiological and human psychophysical responses to mutants of the sweet protein brazzein: delineating brazzein sweetness. Chem Senses 28: 491–498, 2003.
Li X, Li W, Mascioli KJ, Bachmanov AA, Tordoff MG, Epple G, Beauchamp GK, and Reed DR. Comparative analysis of the T1R taste receptor genes in primates. Chem Senses 28: A85, 2003.
Li X, Staszewski L, Xu H, Durick K, Zoller M, and Adler E. Human receptors for sweet and umami taste. Proc Natl Acad Sci USA 99: 4692–4696, 2002.
Liao J and Schultz PG. Three sweet receptor genes are clustered in human chromosome 1. Mamm Genome 14: 291–301, 2003.[CrossRef][ISI][Medline]
Mansfield K. Marmoset models commonly used in biomedical research. Comp Med 53: 383–392, 2003.[ISI][Medline]
Nelson G, Hoon MA, Chandrashekar J, Zhang Y, Ryba NJ, and Zuker CS. Mammalian sweet taste receptors. Cell 106: 381–390, 2001.[CrossRef][ISI][Medline]
Nofre C, Tinti JM, and Glaser D. Evolution of the sweetness receptor in primates. II. Gustatory responses of non-human primates to nine compounds known to be sweet in man. Chem Senses 21: 747–762, 1996.
Perez C, Lucas F, and Sclafani A. Increased flavor acceptance and preference conditioned by the postingestive actions of glucose. Physiol Behav 64: 483–492, 1998.[CrossRef][Medline]
Schiffman SS, Booth BJ, Losee ML, Pecore SD, and Warwick ZS. Bitterness of sweeteners as a function of concentration. Brain Res Bul 36: 505–513, 1995.[CrossRef][ISI][Medline]
Schiffman SS, Hornack K, and Reilly D. Increased taste thresholds of amino acids with age. Am J Clinical Nutrition 32: 1622–1627, 1979.
Scott TR and Giza BK. Coding channels in the taste system of the rat. Science. 249: 1585–1587, 1990.
Zhang Y, Hoon MA, Chandrashekar J, Mueller KL, Cook B, Wu D, Zuker CS, and Ryba NJ. Coding of sweet, bitter, and umami tastes: different receptor cells sharing similar signaling pathways. Cell 112: 293–301, 2003.[CrossRef][ISI][Medline]
Zhao GQ, Zhang Y, Hoon MA, Chandrashekar J, Erlenbach I, Ryba NJ, and Zuker CS. The receptors for mammalian sweet and umami taste. Cell 115: 255–266, 2003.[CrossRef][ISI][Medline]
Zuhlke U and Weinbauer G. The common marmoset (Callithrix jacchus) as a model in toxicology. Toxicol Pathol 31 Suppl: 123–127, 2003.
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  B. Gordesky-Gold, N. Rivers, O. M. Ahmed, and P. A.S. Breslin Drosophila melanogaster Prefers Compounds Perceived Sweet by Humans Chem Senses, March 1, 2008; 33(3): 301 - 309. [Abstract] [Full Text] [PDF]
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