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Here we assessed how intake reductions induced by Roux-en-Y gastric bypass surgery (RYGB) occur within and across access periods by examining drinking microstructure. After training, RYGB (n = 8-10) or sham-operated (SHAM, n = 12) rats were given 60-min access first to 0.3 M sucrose, then to 5% Intralipid, and finally to milk-chocolate Ensure Plus across 5 days each. Initially, total licks taken during the first meal of sucrose and Intralipid by RYGB and SHAM rats did not differ, but, across subsequent test periods, RYGB rats licked less than SHAM rats. First Ensure meal size also did not differ between RYGB and SHAM rats, but SHAM rats increased licking across test periods while the behavior of RYGB rats remained stable. The intake differences between the surgical groups, when they occurred, were most often due to smaller burst sizes in RYGB rats. Importantly, the surgical-group difference in sucrose and Intralipid intakes could not be explained by altered palatability of these solutions because, throughout testing, both groups had similar early meal licking behavior thought to represent the motivational potency of stimulus orosensory features. Although, overall, RYGB rats displayed lower early meal licking of Ensure relative to the SHAM rats, this appeared to be driven primarily by increases in the latter group across test periods; the RYGB group stayed relatively stable. Collectively, these results suggest that some level of postoral experience with these stimuli and/or their components is necessary before intake differences emerge between surgical groups, and, even when differences occur, often immediate taste-motivated ingestive behavior remains unaltered., (Copyright © 2015 the American Physiological Society.)

After Roux-en-Y gastric bypass (RYGB) surgery, patients report consuming fewer fatty and dessert-like foods, and rats display blunted sugar and fat preferences. Here we used a progressive ratio (PR) task in our rat model to explicitly test whether RYGB decreases the willingness of rats to work for very small amounts of preferred sugar- and/or fat-containing fluids. In each of two studies, two groups of rats - one maintained on a high-fat diet (HFD) and standard chow (CHOW) and one given CHOW alone - were trained while water-deprived to work for water or either Ensure or 1.0M sucrose on increasingly difficult operant schedules. When tested before surgery while nondeprived, HFD rats had lower PR breakpoints (number of operant responses in the last reinforced ratio) for sucrose, but not for Ensure, than CHOW rats. After surgery, at no time did rats given RYGB show lower breakpoints than SHAM rats for Ensure, sucrose, or when 5% Intralipid served postoperatively as the reinforcer. Nevertheless, RYGB rats showed blunted preferences for these caloric fluids versus water in 2-bottle preference tests. Importantly, although the Intralipid and sucrose preferences of RYGB rats decreased further over time, subsequent breakpoints for them were not significantly impacted. Collectively, these data suggest that the observed lower preferences for normally palatable fluids after RYGB in rats may reflect a learned adjustment to altered postingestive feedback rather than a dampening of the reinforcing taste characteristics of such stimuli as measured by the PR task in which postingestive stimulation is negligible., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Rats display stereotypical oromotor and somatic responses to small volumes of intraorally infused taste solutions. These behaviors, known as taste reactivity, are categorized by their association with ingestion or rejection and are thought to reflect the palatability of the stimulus. Because supracollicular decerebrate rats display normal taste reactivity responses, it would appear that forebrain structures are not necessary for generating them. However, because moving the plane of transection rostrally, or damaging or manipulating specific ventral forebrain sites disrupts normal taste reactivity behavior, lesions of the gustatory cortex, a region that has been suggested to be involved with palatability processing, may do the same. In the current study, rats received two injections of either ibotenic acid (N=12) or vehicle (N=8), targeting the conventionally defined gustatory cortex in each hemisphere, and were implanted with intraoral cannulae. Following recovery, their responses to intraoral infusions (0.23ml in 1min) of dH2O, sucrose (1.0M and 0.1M), and quinine hydrochloride (3mM and 0.3mM) were video recorded. Analysis of brains with sufficient bilateral lesions (N=10) revealed that, on average, approximately 94% of the gustatory cortex was destroyed. These extensive bilateral lesions had no significant effect on taste reactivity; the numbers of ingestive and aversive responses to sucrose and quinine were similar between groups. Though these findings do not rule out involvement of the gustatory cortex in palatability processing, they make evident that the region of insular cortex destroyed is not necessary for the normal expression of unconditioned affective behavioral responses to taste stimuli., (Copyright © 2015 Elsevier B.V. All rights reserved.)

In recent years, to circumvent the interpretive limitations associated with intake tests commonly used to assess taste function in rodents, investigators have developed devices called gustometers to deliver small volumes of taste samples and measure immediate responses, thereby increasing confidence that the behavior of the animal is under orosensory control. Most of these gustometers can be used to measure unconditioned licking behavior to stimuli presented for short durations and/or can be used to train the animal to respond to various fluid stimuli differentially so as to obtain a reward and/or avoid punishment. Psychometric sensitivity and discrimination functions can thus be derived. Here, we describe a new gustometer design, successfully used in behavioral experiments, that was guided by our experience with an older version used for over 2 decades. The new computer-controlled gustometer features no dead space in stimulus delivery lines, effective cleaning of the licking substrate, and the ability to measure licking without passing electrical current through the animal. The parts and dimensions are detailed, and the benefits and limitations of certain design features are discussed. Schematics for key circuits are provided as supplemental information. Accordingly, it should be possible to fabricate this device in a fashion customized for one's needs., (© The Author 2015. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

While studies of the gustatory cortex (GC) mostly focus on its role in taste aversion learning and memory, the necessity of GC for other fundamental taste-guided behaviors remains largely untested. Here, rats with either excitotoxic lesions targeting GC (n = 26) or sham lesions (n = 14) were assessed for postsurgical retention of a presurgically LiCl-induced conditioned taste aversion (CTA) to 0.1M sucrose using a brief-access taste generalization test in a gustometer. The same animals were then trained in a two-response operant taste detection task and psychophysically tested for their salt (NaCl or KCl) sensitivity. Next, the rats were trained and tested in a NaCl vs. KCl taste discrimination task with concentrations varied. Rats meeting our histological inclusion criterion had large lesions (resulting in a group averaging 80% damage to GC and involving surrounding regions) and showed impaired postsurgical expression of the presurgical CTA (LiCl-injected, n = 9), demonstrated rightward shifts in the NaCl (0.54 log10 shift) and KCl (0.35 log10 shift) psychometric functions, and displayed retarded salt discrimination acquisition (n = 18), but eventually learned and performed the discrimination comparable to sham-operated animals. Interestingly, the degree of deficit between tasks correlated only modestly, if at all, suggesting that idiosyncratic differences in insular cortex lesion topography were the root of the individual differences in the behavioral effects demonstrated here. This latter finding hints at some degree of interanimal variation in the functional topography of insular cortex. Overall, GC appears to be necessary to maintain normal taste sensitivity to NaCl and KCl and for salt discrimination learning. However, higher salt concentrations can be detected and discriminated by rats with extensive damage to GC suggesting that the other resources of the gustatory system are sufficient to maintain partial competence in these tasks, supporting the view that such basic sensory-discriminative taste functions involve distributed processes among central gustatory structures.

The molecular receptors underlying the purported "umami" taste quality commonly associated with l-glutamate have been controversial. Evidence supports the involvement of the T1R1 + T1R3 heterodimer, a GPCR broadly tuned to l-amino acids, but variants of two mGluRs expressed in taste buds have also been implicated. Using a rigorous psychophysical taste-testing paradigm, we demonstrated impaired, if not eliminated, detection of MSG in WT and T1R1, T1R2, T1R3, and T1R2 + T1R3 KO mice when the contribution of sodium was minimized by the epithelial sodium channel blocker amiloride. When inosine 5'-monophosphate (IMP), a ribonucleotide that potentiates the l-glutamate signal through the T1R1 + T1R3 heterodimer, was added, the WT and T1R2 KO mice were able to detect the compound stimulus across all MSG (+amiloride) concentrations due, in part, to the taste of IMP. In contrast, mice lacking T1R1 or T1R3 could not detect IMP alone, yet some were able to detect MSG + amiloride + IMP, but only at the higher MSG concentrations. Interestingly, the sensitivity of T1R1 KO mice to another l-amino acid, lysine, was unimpaired, suggesting that some l-amino acids can be detected through T1R1 + T1R3-independent receptors without sensitivity loss. Given that IMP is not thought to affect mGluRs, behavioral detection of l-glutamate appears to require the contribution of the T1R1 + T1R3 receptor. However, the partial competence observed in some T1R1 and T1R3 KO mice when MSG + amiloride + IMP was tested suggests that a T1R1 or T1R3 homodimer or an unidentified protein, perhaps in conjunction with T1R1 or T1R3, can serve as a low-affinity taste receptor for l-glutamate in the presence of IMP., (Copyright © 2014 the authors 0270-6474/14/3413234-12$15.00/0.)

Systemic blockade of serotonin (5HT) reuptake with paroxetine has been shown to increase sensitivity to sucrose and quinine in humans. Here, using a 2-response operant taste detection task, we measured the effect of paroxetine and the 5HT1A receptor antagonist WAY100635 on the ability of rats to discriminate sucrose, NaCl, and citric acid from water. After establishing individual psychometric functions, 5 concentrations of each taste stimulus were chosen to represent the dynamic portion of the concentration-response curve, and the performance of the rats to these stimuli was assessed after vehicle, paroxetine (7mg/kg intraperitoneally), and WAY100635 (0.3mg/kg subcutaneously; 1mg/kg intravenously) administration. Although, at times, overall performance across concentrations dropped, at most, 5% from vehicle to drug conditions, no differences relative to vehicle were seen on the parameters of the psychometric function (asymptote, slope, or EC50) after drug administration. In contrast to findings in humans, our results suggest that modulation of 5HT activity has little impact on sucrose detectability at perithreshold concentrations in rats, at least at the doses used in this task. In the rat model, the purported paracrine/neurocrine action of serotonin in the taste bud may work in a manner that does not impact overt taste detection behavior., (© The Author 2014. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Remarkably, when lingual gustatory nerves are surgically rerouted to inappropriate taste fields in the tongue, some taste functions recover. We previously demonstrated that quinine-stimulated oromotor rejection reflexes and neural activity (assessed by Fos immunoreactivity) in subregions of hindbrain gustatory nuclei were restored if the posterior tongue, which contains receptor cells that respond strongly to bitter compounds, was cross-reinnervated by the chorda tympani nerve. Such functional recovery was not seen if instead, the anterior tongue, where receptor cells are less responsive to bitter compounds, was cross-reinnervated by the glossopharyngeal nerve, even though this nerve typically responds robustly to bitter substances. Thus, recovery depended more on the taste field being reinnervated than on the nerve itself. Here, the distribution of quinine-stimulated Fos-immunoreactive neurons in two taste-associated forebrain areas was examined in these same rats. In the central nucleus of the amygdala (CeA), a rostrocaudal gradient characterized the normal quinine-stimulated Fos response, with the greatest number of labeled cells situated rostrally. Quinine-stimulated neurons were found throughout the gustatory cortex, but a "hot spot" was observed in its anterior-posterior center in subregions approximating the dysgranular/agranular layers. Fos neurons here and in the rostral CeA were highly correlated with quinine-elicited gapes. Denervation of the posterior tongue eliminated, and its reinnervation by either nerve restored, numbers of quinine-stimulated labeled cells in the rostralmost CeA and in the subregion approximating the dysgranular gustatory cortex. These results underscore the remarkable plasticity of the gustatory system and also help clarify the functional anatomy of neural circuits activated by bitter taste stimulation., (© 2014 Wiley Periodicals, Inc.)

Gustatory cortex (GC), an assemblage of taste-responsive neurons in insular cortex, is widely regarded as integral to conditioned taste aversion (CTA) retention, a link that has been primarily established using lesion approaches in rats. In contrast to this prevailing view, we found that even the most complete bilateral damage to GC produced by ibotenic acid was insufficient to disrupt postsurgical expression of a presurgical CTA; nor were such lesions sufficient to disrupt postsurgical acquisition and initial expression of a second CTA. However, some rats with lesions were significantly impaired on these tests. Further examination of all conditioned rats with lesions, regardless of the lesion topography, revealed a significant positive association between damage in the posterior portion of GC and especially within adjacent posterior regions of insular cortex. Accordingly, we developed a high-resolution lesion-mapping program that permitted the overlay of the individual lesion maps from rats with CTA impairments to produce a groupwise aggregate lesion map. Comparison of this map with one derived from the unimpaired counterparts indicated a specific lesion "hot spot" associated with CTA deficits that included the most posterior end of GC and overlying granular layer and encompassed an area provisionally referred to in the literature as visceral cortex. Thus, the detailed mapping of the lesion in behaviorally defined subgroups of rats allowed us to exploit the variability in performance to uncloak an important potential component of the functional topography of insular cortex; such an approach could have general applicability to other brain structure-function endeavors as well.

Although damage to gustatory cortex (GC) in the rat has been reported to severely impair, if not eliminate, retention of a presurgically conditioned taste aversion (CTA), it has equivocal effects on taste preference as measured by intake tests. Because intake tests can be influenced by nongustatory (e.g., postingestive) factors, we employed the brief-access taste test to assess the effects of ibotenic acid-induced lesions targeting the GC on unconditioned licking to a sucrose and then a quinine concentration series in a specialized lickometer. As a functional lesion assessment, a presurgical CTA to 0.1M NaCl was established in thirsty rats by following 15-min intake with intraperitoneal administration of either LiCl (or NaCl for control) on 2 occasions. Both conditioned sham-operated (SHAM) rats and rats with histologically confirmed extensive damage to the GC (GCX) avoided a NaCl concentration series relative to unconditioned controls in a postsurgical brief-access CTA test, with no difference between the surgical groups in their responses to NaCl or similar concentrations of KCl. GCX rats also did not differ from SHAM rats in the EC50 of concentration-response functions for sucrose or quinine. Clearly, the critical cortical area required for the retention of a presurgical CTA falls outside of the extensive area of damage, which was well centered within the conventionally defined gustatory zone of the insular cortex. The absence of an effect on unconditioned responsiveness to sucrose and quinine suggests that the damaged region is also unnecessary for the normal expression of affective licking responses to tastants.

Objective: To determine whether rats reaching the same body mass, having been fed either a low-fat (LFD) or a high-fat diet (HFD), differ in white adipose tissue (WAT) deposition., Methods: In experiment 1, 22 Sprague-Dawley rats of the same age were divided into 11 rats with body mass below the batch median and fed a HFD, and 11 above the median and fed a LFD. In experiment 2, 20 Sprague-Dawley rats of the same age and starting body mass were randomised to either a HFD or LFD. When all groups reached similar final body mass, WAT was quantified using magnetic resonance imaging (MRI), dissection, and plasma leptin., Results: In experiment 1, both groups reached similar final body mass at the same age; in experiment 2 the HFD group reached similar final body mass earlier than the LFD group. There were no significant differences in WAT as assessed by MRI or leptin between the HFD and LFD groups in both experiments. Dissection revealed a trend for higher retroperitoneal and epididymal adiposity in the HFD groups in both experiments., Conclusions: We conclude that at similar body mass, adiposity is independent of the macronutrient composition of the feeding regimen used to achieve it., (© 2014 S. Karger GmbH, Freiburg.)

Background: The consumption of high fat and sugar diets is decreased after gastric bypass surgery (GB). The mechanisms remain unclear, with tests of motivated behavior toward fat and sugar producing conflicting results in a rat model. These discrepancies may be due to differences in presurgical maintenance diets. The authors used their GB rat model to determine whether the fat content of preoperative maintenance diets affects weight loss, calorie intake, and macronutrient selection after surgery., Methods: Male Wistar rats were either low-fat diet fed (LFDF) with normal chow or high-fat diet fed (HFDF) before randomization to GB or sham surgery. In food preference test 1, the animals were offered the choice of a vegetable drink (V8) or a high-calorie liquid (Ensure), and in food preference test 2, they could choose normal chow or a solid high-fat diet., Results: The GB groups did not differ significantly in terms of body weight loss or caloric intake. In food preference test 1, both groups responded similarly by reducing their preference for Ensure and increasing their preference for V8. In food preference test 2, the HFDF-GB rats reduced their preference for a solid high-fat diet gradually compared with the immediate reduction observed in the LFDF-GB rats., Conclusion: The consumption of presurgical maintenance diets with different fat contents did not affect postoperative weight loss outcomes. Both the LFDF-GB and HFDF-GB rats exhibited behaviors consistent with the possible expression of a conditioned taste aversion to a high-fat stimulus. These results suggest that for some physiologic parameters, low-fat-induced obesity models can be used for the study of changes after GB and have relevance to many obese humans who consume high-calorie but low-fat diets.

Background: Many active pharmaceutical ingredients taste bitter and thus are aversive to children as well as many adults. Encapsulation of the medicine in pill or tablet form, an effective method for adults to avoid the unpleasant taste, is problematic for children. Many children cannot or will not swallow solid dose forms., Objective: This review highlights basic principles of gustatory function, with a special focus on the science of bitter taste, derived from studies of animal models and human psychophysics. We focus on the set of genes that encode the proteins that function as bitter receptors as well as the cascade of events that leads to multidimensional aspects of taste function, highlighting the role that animal models played in these discoveries. We also summarize psychophysical approaches to studying bitter taste in adult and pediatric populations, highlighting evidence of the similarities and differences in bitter taste perception and acceptance between adults and children and drawing on useful strategies from animal models., Results: Medicine often tastes bitter, and because children are more bitter-sensitive than are adults, this creates problems with compliance. Bitter arises from stimulating receptors in taste receptor cells, with signals processed in the taste bud and relayed to the brain. However, there are many gaps in our understanding of how best to measure bitterness and how to ameliorate it, including whether it is more efficiently addressed at the level of receptor and sensory signaling, at the level of central processing, or by masking techniques. All methods of measuring responsiveness to bitter ligands-in animal models through human psychophysics or with "electronic tongues"-have limitations., Conclusions: Better-tasting medications may enhance pediatric adherence to drug therapy. Sugars, acids, salt, and other substances reduce perceived bitterness of several pharmaceuticals, and although pleasant flavorings may help children consume some medicines, they often are not effective in suppressing bitter tastes. Further development of psychophysical tools for children will help us better understand their sensory worlds. Multiple testing strategies will help us refine methods to assess acceptance and compliance by various pediatric populations. Research involving animal models, in which the gustatory system can be more invasively manipulated, can elucidate mechanisms, ultimately providing potential targets. These approaches, combined with new technologies and guided by findings from clinical studies, will potentially lead to effective ways to enhance drug acceptance and compliance in pediatric populations., (© 2013 Elsevier HS Journals, Inc. All rights reserved.)

Increased serotonergic activity has been shown to reduce motivation to ingest, which may involve, in part, gustatory processes. Here, we examined the effect of paroxetine, a selective serotonin reuptake inhibitor, on appetitive responding for a preferred and an avoided taste solution using a progressive ratio (PR) task in which licking was employed as the operant. Male Sprague-Dawley rats (n = 8/taste stimulus) were trained to respond for a concentration series of sucrose or quinine on fixed and PR schedules of reinforcement. Performance for sucrose was assessed while the rats were partially food- and water-restricted and nondeprived, and performance for water and quinine was assessed while the rats were water-deprived. Then, the rats were injected with vehicle (10% dimethyl sulfoxide, 1mL/kg intraperitoneal [ip], -1h) or paroxetine (5mg/kg), and their responding on a PR schedule for sucrose measured when the rats were nondeprived or for water and quinine when the rats were water-deprived. Paroxetine decreased breakpoint, which was defined as the number of operant (e.g., dry) licks in the final reinforced ratio, for water, quinine, and sucrose. This demonstrates that a general systemic increase in serotonergic activity decreases the appetitive-based responses to both preferred and nonpreferred fluids under different deprivation states.

In rodents, at least two transduction mechanisms are involved in salt taste: 1) the sodium-selective epithelial sodium channel, blocked by topical amiloride administration, and 2) one or more amiloride-insensitive cation-nonselective pathways. Whereas electrophysiological evidence from the chorda tympani nerve (CT) has implicated the transient receptor potential vanilloid-1 (TRPV1) channel as a major component of amiloride-insensitive salt taste transduction, behavioral results have provided only equivocal support. Using a brief-access taste test, we examined generalization profiles of water-deprived C57BL/6J (WT) and TRPV1 knockout (KO) mice conditioned (via LiCl injection) to avoid 100 μM amiloride-prepared 0.25 M NaCl and tested with 0.25 M NaCl, sodium gluconate, KCl, NH(4)Cl, 6.625 mM citric acid, 0.15 mM quinine, and 0.5 M sucrose. Both LiCl-injected WT and TRPV1 KO groups learned to avoid NaCl+amiloride relative to controls, but their generalization profiles did not differ; LiCl-injected mice avoided the nonsodium salts and quinine suggesting that a TRPV1-independent pathway contributes to the taste quality of the amiloride-insensitive portion of the NaCl signal. Repeating the experiment but doubling all stimulus concentrations revealed a difference in generalization profiles between genotypes. While both LiCl-injected groups avoided the nonsodium salts and quinine, only WT mice avoided the sodium salts and citric acid. CT responses to these stimuli and a concentration series of NaCl and KCl with and without amiloride did not differ between genotypes. Thus, in our study, TRPV1 did not appear to contribute to sodium salt perception based on gustatory signals, at least in the CT, but may have contributed to the oral somatosensory features of sodium.

It has been suggested that the weight loss seen in individuals who receive Roux-en-Y gastric bypass surgery may be due, at least in part, to changes in patient food selection, and that this change may stem from effects of the operation on the sense of taste. In this review, we evaluate the literature examining postoperative changes in food intake and food choice. While some evidence suggests that gastric bypass leads to altered food selection and taste perceptions, a clear picture regarding these changes remains to be elucidated and is blurred by inconsistencies, which may be rooted in the diverse subject pools within and between studies as well as in the indirect measures used to assess ingestive behavior. We argue that complementing current assessment tools with more direct measures of intake, food selection, and taste-related behavior might help provide some clarity and also facilitate translation between findings from animal models, in which similar measures are available, and clinical research., (Copyright © 2012 Elsevier Inc. All rights reserved.)

The contribution of orosensory signals, especially taste, on body mass, and feeding and drinking patterns in the rat was examined. Gustatory deafferentation was produced by bilateral transection of the chorda tympani, glossopharyngeal, and greater superficial petrosal nerves. Total calories consumed from sweetened-milk diet and oil-chow mash by the nerve-transected rats significantly decreased relative to sham-operated controls, mostly attributable to decreases in bout number, but not size. Nevertheless, caloric intake steadily increased over the postsurgical observation period, but body mass remained below both presurgical baseline and control levels and did not significantly increase over this time. After the sweetened-milk diet/oil-chow mash phase, rats received a series of sucrose preference tests. Interestingly, the nerve-transected rats preferred sucrose, and intake did not differ from controls, likely due to the stimulus sharing some nontaste chemosensory properties with the sweetened-milk diet. The neurotomized rats initiated a greater number of sucrose-licking bouts that were smaller in size and slower in licking rate, compared with control rats, and, unlike in control rats, the latter two bout parameters did not vary across concentration. Thus, in the absence of gustatory neural input, body mass is more stable compared with the progressive trajectory of weight gain seen in intact rats, and caloric intake initially decreases but recovers. The consequences of gustatory neurotomy on processes that determine meal initiation (bout number) and meal termination (bout size) are not fixed and appear to be influenced by presurgical experience with food stimuli coupled with its nongustatory chemosensory properties.

Background: Obesity is among the leading causes of disease and death. Bariatric surgery is the most effective treatment of obesity. There is increasing evidence that after gastric bypass surgery, patients and animal models show a decreased preference for sweet and fatty foods. The underlying mechanism may include alterations in taste function., Objective: We hypothesize that a gastric bypass reduces the reward value of sweet and fat tastes., Design: In this prospective case-control study, 11 obese patients who were scheduled to undergo a gastric bypass and 11 normal-weight control subjects in the fed state clicked a computer mouse to receive a sweet and fatty candy on a progressive ratio schedule 10 wk apart (in patients, testing took place 2 wk before and 8 wk after gastric bypass surgery). Subjects worked progressively harder to obtain a food reward (reinforcer) until they stopped clicking (ie, the breakpoint), which was a measure of the reinforcer value. Breakpoints were assessed by the number of mouse clicks in the last completed ratio. The experiment was repeated in a different cohort by using vegetable pieces as the reinforcer., Results: Breakpoints in the test sessions of control subjects correlated highly for both reinforcers. The median breakpoint for candies, but not vegetables, was reduced by 50% in the obese group after gastric bypass. Patients with the largest reduction in the breakpoint had the largest decrease in BMI., Conclusions: Gastric bypass surgery resulted in the selective reduction of the reward value of a sweet and fat tastant. This application of the progressive ratio task provided an objective and reliable evaluation of taste-driven motivated behavior for food stimuli after obesity surgery.

Several methods exist for reliably determining the motivational valence of a taste stimulus in animals, but few to determine its perceptual quality independent of its apparent affective properties. Individual differences in taste preference and acceptability could result from variance in the perceptual qualities of the stimulus leading to different hedonic evaluations. Alternatively, taste perception might be identical across subjects, but the processing of the sensory signals in reward circuits could differ. Using an operant-based taste cue discrimination/generalization task involving a gustometer, we trained male Long-Evans rats to report the degree to which a test stimulus resembled the taste quality of either sucrose or quinine regardless of its intensity. The rats, grouped by a characteristic bimodal phenotypic difference in their preference for sucralose, treated this artificial sweetener as qualitatively different-compared to sucralose-avoiding rats, the sucralose-preferring rats found the stimulus much more perceptually similar to sucrose. Although the possibility that stimulus palatability may have served as a discriminative cue cannot entirely be ruled out, the profile of results suggests otherwise. Subsequent brief-access licking tests revealed that affective licking responses of the same sucralose-avoiding and -preferring rats differed across concentration in a manner approximately similar to that found in the stimulus generalization task. Thus, the perceived taste quality of sucralose alone may be sufficient to drive the observed behavioral avoidance of the compound. By virtue of its potential ability to dissociate the sensory and motivational consequences of a given experimental manipulation on taste-related behavior, this approach could be interpretively valuable.

Evidence in the literature supports the hypothesis that the T1R2+3 heterodimer binds to compounds that humans describe as sweet. Here, we assessed the necessity of the T1R2 and T1R3 subunits in the maintenance of normal taste sensitivity to carbohydrate stimuli. We trained and tested water-restricted T1R2 knockout (KO), T1R3 KO and their wild-type (WT) same-sex littermate controls in a two-response operant procedure to sample a fluid and differentially respond on the basis of whether the stimulus was water or a tastant. Correct responses were reinforced with water and incorrect responses were punished with a time-out. Testing was conducted with a modified descending method of limits procedure across daily 25-min sessions. Both KO groups displayed severely impaired performance and markedly decreased sensitivity when required to discriminate water from sucrose, glucose, or maltose. In contrast, when Polycose was tested, KO mice had normal EC(50) values for their psychometric functions, with some slight, but significant, impairment in performance. Sensitivity to NaCl did not differ between these mice and their WT controls. Our findings support the view that the T1R2+3 heterodimer is the principal receptor that mediates taste detection of natural sweeteners, but not of all carbohydrate stimuli. The combined presence of T1R2 and T1R3 appears unnecessary for the maintenance of relatively normal sensitivity to Polycose, at least in this task. Some detectability of sugars at high concentrations might be mediated by the putative polysaccharide taste receptor, the remaining T1R subunit forming either a homodimer or heteromer with another protein(s), or nontaste orosensory cues.

Roux-en-Y gastric bypass (RYGB) surgery has been shown to decrease consummatory responsiveness of rats to high sucrose concentrations, and genetic deletion of glucagon-like peptide-1 receptors (GLP-1R) has been shown to decrease consummatory responsiveness of mice to low-sucrose concentrations. Here we assessed the effects of RYGB and pharmacological GLP-1R modulation on sucrose licking by chow-fed rats in a brief-access test that assessed consummatory and appetitive behaviors. Rats were tested while fasted presurgically and postsurgically and while nondeprived postsurgically and 5 h after intraperitoneal injections with the GLP-1R antagonist exendin-3(9-39) (30 μg/kg), agonist exendin-4 (1 μg/kg), and vehicle in 30-min sessions during which a sucrose concentration series (0.01-1.0 M) was presented in 10-s trials. Other rats were tested postsurgically or 15 min after peptide or vehicle injection while fasted and while nondeprived. Independent of food-deprivation state, sucrose experience, or GLP-1R modulation, RYGB rats took 1.5-3× as many trials as sham-operated rats, indicating increased appetitive behavior. Under nondeprived conditions, RYGB rats with presurgical sucrose experience licked more to sucrose relative to water compared with sham-operated rats. Exendin-4 and exendin-3(9-39) impacted 0.3 M sucrose intake in a one-bottle test, but never interacted with surgical group to affect brief-access responding. Unlike prior reports in both clearly obese and relatively leaner rats given RYGB and in GLP-1R knockout mice, we found that neither RYGB nor GLP-1R blockade decreased consummatory responsiveness to sucrose in our less obese chow-fed rats. Collectively, these results highlight the fact that changes in taste-driven motivated behavior to sucrose after RYGB and/or GLP-1R modulation are very model and measure dependent.

Intracellular Cl(-) concentrations ([Cl(-)](i)) of sensory neurons regulate signal transmission and signal amplification. In dorsal root ganglion (DRG) and olfactory sensory neurons (OSNs), Cl(-) is accumulated by the Na(+)-K(+)-2Cl(-) cotransporter 1 (NKCC1), resulting in a [Cl(-)](i) above electrochemical equilibrium and a depolarizing Cl(-) efflux upon Cl(-) channel opening. Here, we investigate the [Cl(-)](i) and function of Cl(-) in primary sensory neurons of trigeminal ganglia (TG) of wild type (WT) and NKCC1(-/-) mice using pharmacological and imaging approaches, patch-clamping, as well as behavioral testing. The [Cl(-)](i) of WT TG neurons indicated active NKCC1-dependent Cl(-) accumulation. Gamma-aminobutyric acid (GABA)(A) receptor activation induced a reduction of [Cl(-)](i) as well as Ca(2+) transients in a corresponding fraction of TG neurons. Ca(2+) transients were sensitive to inhibition of NKCC1 and voltage-gated Ca(2+) channels (VGCCs). Ca(2+) responses induced by capsaicin, a prototypical stimulus of transient receptor potential vanilloid subfamily member-1 (TRPV1) were diminished in NKCC1(-/-) TG neurons, but elevated under conditions of a lowered [Cl(-)](o) suggesting a Cl(-)-dependent amplification of capsaicin-induced responses. Using next generation sequencing (NGS), we found expression of different Ca(2+)-activated Cl(-) channels (CaCCs) in TGs of mice. Pharmacological inhibition of CaCCs reduced the amplitude of capsaicin-induced responses of TG neurons in Ca(2+) imaging and electrophysiological recordings. In a behavioral paradigm, NKCC1(-/-) mice showed less avoidance of the aversive stimulus capsaicin. In summary, our results strongly argue for a Ca(2+)-activated Cl(-)-dependent signal amplification mechanism in TG neurons that requires intracellular Cl(-) accumulation by NKCC1 and the activation of CaCCs.

The discovery of the T1R family of Class C G protein-coupled receptors in the peripheral gustatory system a decade ago has been a tremendous advance for taste research, and its conceptual reach has extended to other organ systems. There are three proteins in the family, T1R1, T1R2, and T1R3, encoded by their respective genes, Tas1r1, Tas1r2, and Tas1r3. T1R2 combines with T1R3 to form a heterodimer that binds with sugars and other sweeteners. T1R3 also combines with T1R1 to form a heterodimer that binds with l-amino acids. These proteins are expressed not only in taste bud cells, but one or more of these T1Rs have also been identified in the nasal epithelium, gut, pancreas, liver, kidney, testes and brain in various mammalian species. Here we review current perspectives regarding the functional role of these receptors, concentrating on sweet taste and feeding. We also discuss behavioral findings suggesting that a glucose polymer mixture, Polycose, which rodents avidly prefer, appears to activate a receptor that does not depend on the combined expression of T1R2 and T1R3. In addition, although the T1Rs have been implicated as playing a role in glucose sensing, T1R2 knock-out (KO) and T1R3 KO mice display normal chow and fluid intake as well as normal body weight compared with same-sex littermate wild type (WT) controls. Moreover, regardless of whether they are fasted or not, these KO mice do not differ from their WT counterparts in their Polycose intake across a broad range of concentrations in 30-minute intake tests. The functional implications of these results and those in the literature are considered., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Roux-en-Y gastric bypass (gastric bypass) patients reportedly have changes in perception and consumption of sweet-tasting foods. This study aimed to further investigate alterations in sweet food intake in rats and sucrose detection in humans after gastric bypass. Wistar rats were randomized to gastric bypass or sham-operations and preference for sucrose (sweet), sodium chloride (salty), citric acid (sour) and quinine hydrochloride (bitter) was assessed with standard two-bottle intake tests (vs. water). Intestinal T1R2 and T1R3 expression and plasma levels of glucagon-like-peptide 1 (GLP-1) and peptide YY (PYY) were measured. Furthermore, obese patients and normal weight controls were tested for sucrose taste detection thresholds pre- and postoperatively. Visual analogue scales measuring hedonic perception were used to determine the sucrose concentration considered by patients and controls as "just about right" pre- and postoperatively. Gastric bypass reduced the sucrose intake relative to water in rats (p<0.001). Preoperative sucrose exposure reduced this effect. Preference or aversion for compounds representative of other taste qualities in naïve rats remained unaffected. Intestinal T1R2 and T1R3 expression was significantly decreased in the alimentary limb while plasma levels of GLP-1 and PYY were elevated after bypass in rats (p=0.01). Bypass patients showed increased taste sensitivity to low sucrose concentrations compared with controls (p<0.05), but both groups considered the same sucrose concentration as "just about right" postoperatively. In conclusion, gastric bypass reduces sucrose intake relative to water in sucrose-naïve rats, but preoperative sucrose experience attenuates this effect. Changes in sucrose taste detection do not predict hedonic taste ratings of sucrose in bypass patients which remain unchanged. Thus, factors other than the unconditional affective value of the taste may also play a role in determining food preferences after gastric bypass., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Roux-en-Y gastric bypass is the most effective therapy for morbid obesity. This study investigated how gastric bypass affects intake of and preference for high-fat food in an experimental (rat) study and within a trial setting (human). Proportion of dietary fat in gastric bypass patients was significantly lower 6 yr after surgery compared with patients after vertical-banded gastroplasty (P = 0.046). Gastric bypass reduced total fat and caloric intake (P < 0.001) and increased standard low-fat chow consumption compared with sham controls (P < 0.001) in rats. Compared with sham-operated rats, gastric bypass rats displayed much lower preferences for Intralipid concentrations > 0.5% in an ascending concentration series (0.005%, 0.01%, 0.05%, 0.1%, 0.5%, 1%, 5%) of two-bottle preference tests (P = 0.005). This effect was demonstrated 10 and 200 days after surgery. However, there was no difference in appetitive or consummatory behavior in the brief access test between the two groups (P = 0.71) using similar Intralipid concentrations (0.005% through 5%). Levels of glucagon-like peptide-1 (GLP-1) were increased after gastric bypass as expected. An oral gavage of 1 ml corn oil after saccharin ingestion in gastric bypass rats induced a conditioned taste aversion. These findings suggest that changes in fat preference may contribute to long-term maintained weight loss after gastric bypass. Postingestive effects of high-fat nutrients resulting in conditioned taste aversion may partially explain this observation; the role of GLP-1 in mediating postprandial responses after gastric bypass requires further investigation.

Although it is clear that the heterodimer formed by the T1R2 and T1R3 proteins serves as the primary taste receptor for sweeteners, there is growing evidence that responses to glucose polymers may be mediated by a different taste receptor. Here we report that although T1R2 knock-out (KO) and T1R3 KO mice displayed severely impaired responding to glucose, maltose, and maltotriose in an initial session of a brief-access taste test (5 s trials, 25 min sessions) relative to wild-type (WT) mice, they subsequently increased their licking as a function of concentration for maltose and maltotriose with continued testing, presumably due to associating weak oral cues with positive post-ingestive consequences. Interestingly, these KO mice displayed relatively normal concentration-dependent licking to Polycose, a mixture of glucose polymers, even in the first session. Importantly, the experience-dependent increase in responsiveness to the sugars observed with the T1R2 and T1R3 single KO mice was not statistically significant in the T1R2/3 double KO mice. The double KO mice, however, still displayed significant concentration-dependent responding to Polycose in the first test session, albeit lick rates were slightly lower than those seen for WT mice, perhaps because small amounts of glucose, maltose, and maltotriose found in Polycose were enhancing the signal in WT mice or because T1R2 or T1R3 can possibly heteromerize with another protein to form a fully functional glucose polymer receptor. These findings provide behavioral evidence that glucose polymers, with an optimal chain length greater than three glucose moieties, stimulate a taste receptor independent of the T1R2+3 heterodimer.

Serotonin and the 5HT(1A) receptor are expressed in a subset of taste receptor cells, and the 5HT(3) receptor is expressed on afferent fibers innervating taste buds. Exogenous administration of the selective serotonin reuptake inhibitor, paroxetine, has been shown to increase taste sensitivity to stimuli described by humans as sweet and bitter. Serotonergic agonists also decrease food and fluid intake, and it is possible that modulations of serotonin may alter taste-based hedonic responsiveness; alternatively, or in combination, serotonin may interact with physiological state to impact ingestive behavior. In this study, the unconditioned licking of prototypical taste stimuli by rats in brief-access taste tests was assessed following paroxetine administration (0.3-10 mg/kg intraperitoneal). We also measured sucrose licking by rats in different deprivation states after paroxetine (5 mg/kg). In neither experiment did we find any evidence of an effect of paroxetine on licking relative to water to any of the taste stimuli in the brief-access test at doses that decreased food intake. However, in some conditions, paroxetine decreased trials initiated to tastants. Therefore, a systemic increase in serotonin via paroxetine administration can decrease appetitive behavior in brief-access tests but is insufficient to alter taste-guided consummatory behavior., (© The Author 2011. Published by Oxford University Press. All rights reserved.)

Evidence in the literature shows that in rodents, some taste-responsive neurons respond to both quinine and acid stimuli. Also, under certain circumstances, rodents display some degree of difficulty in discriminating quinine and acid stimuli. Here, C57BL/6J mice were trained and tested in a 2-response operant discrimination task. Mice had severe difficulty discriminating citric acid from quinine and 6-n-propylthiouracil (PROP) with performance slightly, but significantly, above chance. In contrast, mice were able to competently discriminate sucrose from citric acid, NaCl, quinine, and PROP. In another experiment, mice that were conditioned to avoid quinine by pairings with LiCl injections subsequently suppressed licking responses to quinine and citric acid but not to NaCl or sucrose in a brief-access test, relative to NaCl-injected control animals. However, mice that were conditioned to avoid citric acid did not display cross-generalization to quinine. These mice significantly suppressed licking only to citric acid, and to a much lesser extent NaCl, compared with controls. Collectively, the findings from these experiments suggest that in mice, citric acid and quinine share chemosensory features making discrimination difficult but are not perceptually identical.

Recent evidence in the literature suggests that signals carried by the glossopharyngeal nerve (GL), which supplies sensory and parasympathetic innervation of the posterior tongue, might be essential in the maintenance of normal gustatory responses to fat stimuli. Here, we report that GL transection (GLX) significantly decreased corn oil intake and preference in 23-h two-bottle tests relative to sham-operated controls (Sham). Drinking-pattern analysis of corn oil licking revealed that bout size, rather than the number of bouts initiated, was smaller in GLX than Sham rats. We also tested a range of glucose concentrations and found that total licks over daily 23-h sessions significantly decreased in GLX compared with Sham rats, but this difference failed to reach significance when intake or any bout parameter was measured. These results show that the signals in the GL normally contribute to processes involved with corn oil bout termination as opposed to bout initiation. GL-derived signals could potentially provide input to "reward" circuits in the ventral forebrain that could serve to maintain ingestion during a meal or, alternatively, could act at the level of the brain stem to attenuate the inhibitory potency of vagal signals, thus delaying the onset of satiation, or perhaps contribute to a cephalic phase reflex modulation of the gut. Parasympathetic efferents in the GL innervating the von Ebner's glands, which secrete lingual lipase, which is thought to break down corn oil into detectable ligands, could also be playing a role in driving corn oil intake. Whatever the mechanism, an intact GL is clearly necessary in maintaining normal intake of corn oil.

Rats lacking input to the chorda tympani (CT) nerve, a facial nerve branch innervating anterior tongue taste buds, show robust impairments in salt discrimination demonstrating its necessity. We tested the sufficiency of the CT for salt taste discrimination and whether the remaining input provided by the greater superficial petrosal (GSP) nerve, a facial nerve branch innervating palatal taste buds, or by the glossopharyngeal (GL) nerve, innervating posterior tongue taste buds, could support performance after extended postsurgical testing. Rats presurgically trained and tested in a two-response operant task to discriminate NaCl from KCl were subjected to sham surgery or transection of the CT (CTx), GL (GLx), or GSP (GSPx), alone or in combination. While initially reduced postsurgically, performance by rats with an intact GSP after CTx + GLx increased to normal over 6 wk of testing. Rats with CTx + GSPx consistently performed near chance levels. In contrast, rats with GSPx + GLx were behaviorally normal. A subset of rats subjected to sham surgery and exposed to lower concentrations during postsurgical testing emulating decreased stimulus intensity after neurotomy showed no significant impairment. These results demonstrate that CTx changes the perceptual nature of NaCl and/or KCl, leading to severe initial postsurgical impairments in discriminability, but a "new" discrimination can be relearned based on the input of the GSP. Despite losing ∼75% of their taste buds, rats are unaffected after GSPx + GLx, demonstrating that the CT is not only necessary, but also sufficient, for maintaining salt taste discrimination, notwithstanding the unlikely contribution of the small percentage of taste receptors innervated by the superior laryngeal nerve.

Forty years have passed since it was demonstrated that a cross-regenerated gustatory nerve in the rat tongue adopts the stimulus-response properties of the taste receptor field it cross-reinnervates. Nevertheless, the functional consequences of channeling peripheral taste signals through inappropriate central circuits remain relatively unexplored. Here we tested whether histologically confirmed cross-regeneration of the chorda tympani nerve (CT) into the posterior tongue in the absence of the glossopharyngeal nerve (GL) (CT-PostTongue) or cross-regeneration of the GL into the anterior tongue in the absence of the CT (GL-AntTongue) would maintain presurgically trained performance in an operant NaCl vs. KCl taste discrimination task in rats. Before surgery all groups were averaging over 90% accuracy. Oral amiloride treatment dropped performance to virtually chance levels. During the first week after surgery, sham-operated rats, GL-transected rats, and rats with regenerated CTs displayed highly competent discrimination performance. In contrast, CT-transected rats were severely impaired (59% accuracy). Both the CT-PostTongue and the GL-AntTongue groups were impaired to a similar degree as CT-transected rats. These initially impaired groups improved their performance over the weeks of postsurgical testing, suggesting that the rats were capable of relearning the task with discriminable signals in the remaining taste nerves. This relearned performance was dependent on input from amiloride-sensitive receptors likely in the palate. Overall, these results suggest that normal competence in a salt discrimination task is dependent on the taste receptor field origin of the input as well as the specific nerve transmitting the signals to its associated circuits in the brain., (Copyright 2009 Elsevier B.V. All rights reserved.)

The act of eating and drinking brings food-related chemicals into contact with taste cells. Activation of these taste cells, in turn, engages neural circuits in the central nervous system that help animals identify foods and fluids, determine what and how much to eat, and prepare the body for digestion and assimilation. Analytically speaking, these neural processes can be divided into at least three categories: stimulus identification, ingestive motivation, and digestive preparation. This review will discuss recent advances in peripheral gustatory mechanisms, primarily from rodent models, in the context of these three major categories of taste function.

The T1R2 and T1R3 proteins are expressed in taste receptor cells and form a heterodimer binding with compounds described as sweet by humans. We examined whether Polycose taste might be mediated through this heterodimer by testing T1R2 knockout (KO) and T1R3 KO mice and their wild-type (WT) littermate controls in a series of brief-access taste tests (25-min sessions with 5-s trials). Sucrose, Na-saccharin, and Polycose were each tested for three consecutive sessions with order of presentation varied among subgroups in a Latin-Square manner. Both KO groups displayed blunted licking responses and initiated significantly fewer trials of sucrose and Na-saccharin across a range of concentrations. KO mice tested after Polycose exposure demonstrated some degree of concentration-dependent licking of sucrose, likely attributable to learning related to prior postingestive experience. These results are consistent with prior findings in the literature, implicating the T1R2+3 heterodimer as the principal taste receptor for sweet-tasting ligands, and also provide support for the potential of postingestive experience to influence responding in the KO mice. In contrast, T1R2 KO and T1R3 KO mice displayed concentration-dependent licking responses to Polycose that tracked those of their WT controls and in some cases licked midrange concentrations more; the number of Polycose trials initiated overall did not differ between KO and WT mice. Thus, the T1R2 and T1R3 proteins are individually unnecessary for normal concentration-dependent licking of Polycose to be expressed in a brief-access test. Whether at least one of these T1R protein subunits is necessary for normal Polycose responsiveness remains untested. Alternatively, there may be a novel taste receptor(s) that mediates polysaccharide taste.

We developed a novel behavioral method, adapted from the work by Morrison (1967), for the assessment of taste quality in rats. Four groups of rats were trained to discriminate a standard stimulus (either NaCl, sucrose, quinine, or citric acid, which are widely thought to represent the four basic human taste qualities of salty, sweet, bitter, and sour, respectively) from the remaining three compounds (each at multiple concentrations). Animals were then tested for generalization to the standard stimuli when test compounds were presented and a quality profile was constructed. Rats generalized novel concentrations of standard stimuli completely to their training concentrations and generalized their responses to mixtures of NaCl and sucrose on the basis of the relative concentrations of the stimulus components. In general, the sugars (at high concentrations), denatonium, tartaric acid, and sodium gluconate generalized to sucrose, quinine, citric acid, and NaCl, respectively. Monosodium glutamate generalized to a mixture of sucrose and NaCl. KCl produced a complex generalization profile with notable quinine and citric acid components. Our procedure supplements the current use of the conditioned taste aversion generalization procedure which has some procedural and interpretive limitations. Although our procedure involves the use of a complex stimulus delivery and response measurement apparatus and requires substantial initial conditioning of animals, once trained, a single cohort of animals can be tested for its response to a substantial number of test stimuli over the course of many months without any ostensible loss of stimulus control.

The greater superficial petrosal nerve (GSP), innervating taste buds in the palate, is known to be exceptionally responsive to sucrose, especially compared with the responsiveness of the chorda tympani nerve (CT). However, whereas transection of the CT (CTX) alone has little or no effect on unconditioned licking responses to many "sweet" stimuli, the impact of GSP transection (GSPX) alone is equivocal. To further examine the role of the GSP on licking responses to putatively sweet-tasting substances, brief-access taste tests were conducted in nondeprived rats before and after sham surgery (SHAM) or CTX or GSPX. A range of concentrations of sucrose, L-alanine, glycine, and L-serine, with and without 1.0 mM inosine monophosphate (IMP) added, were used. All groups showed significant concentration-dependent increases in licking to all stimuli presurgically and postsurgically. CTX decreased licking responses relative to SHAM rats in the first sucrose test. There was also a group x concentration interaction for L-alanine, but post hoc tests did not reveal its basis. Other than this, there were no significant differences among the surgical groups. Interestingly, rats with GSPX tended to initiate fewer trials than SHAM rats. Overall, after GSPX, the remaining gustatory nerves are apparently sufficient to maintain concentration-dependent licking responses to all stimuli tested here. The disparity between our results and others in the literature where GSPX reduced licking responses to sucrose is possibly related to differences in surgical technique or test trial duration.

Studies examining the effects of transection and regeneration of the glossopharyngeal (GL) and chorda tympani (CT) nerves on various taste-elicited behaviors in rats have demonstrated that the GL (but not the CT) nerve is essential for the maintenance of both an unconditioned protective reflex (gaping) and the neural activity observed in central gustatory structures in response to lingual application of a bitter substance. An unresolved issue, however, is whether recovery depends more on the taste nerve and the central circuits that it supplies and/or on the tongue receptor cell field being innervated. To address this question, we experimentally cross-wired these taste nerves, which, remarkably, can regenerate into parts of the tongue they normally do not innervate. We report that quinine-stimulated gaping behavior was fully restored, and neuronal activity, as assessed by Fos immunohistochemistry in the nucleus of the solitary tract and the parabrachial nucleus, was partially restored only if the posterior tongue (PT) taste receptor cell field was reinnervated; the particular taste nerve supplying the input was inconsequential to the recovery of function. Thus, PT taste receptor cells appear to play a privileged role in triggering unconditioned gaping to bitter tasting stimuli, regardless of which lingual gustatory nerve innervates them. Our findings demonstrate that even when a lingual gustatory nerve (the CT) forms connections with taste cells in a non-native receptor field (the PT), unconditioned taste rejection reflexes to quinine can be maintained. These findings underscore the extraordinary ability of the gustatory system to adapt to peripherally reorganized input for particular behaviors.

In taste bud cells, two different T1R heteromeric taste receptors mediate signal transduction of sugars (the canonical "sweet" taste receptor, T1R2 + T1R3) and L-amino acids (the T1R1 + T1R3 receptor). The T1R1 + T1R3 receptor is thought to mediate what is considered the fifth basic taste quality "umami." However, a subset of L-amino acids is "sweet tasting" to humans and appears to possess a "sucrose-like" taste quality to nonhuman mammals. This suggests, to varying degrees, that all of these compounds activate a single neural channel that leads to the perception of sweetness. The experiments detailed here were designed to test the ability of mice to distinguish between sucrose and various others sugars and L-amino acids in operant taste discrimination tasks. Mice had at least some difficulty discriminating sucrose from L-serine, L-threonine, maltose, fructose, and glucose. For example, when concentration effects are taken into consideration, mice discriminated poorly, if at all, sucrose from glucose or fructose and, to a lesser extent maltose, suggesting that sugars generate a unitary perceptual quality. However, mice were able to reliably discriminate sucrose from L-serine and L-threonine. Data gathered using a conditioned taste aversion assay also suggest that, although qualitatively similar to the taste of sucrose, L-serine and L-threonine generate distinctive percepts. In conclusion, it appears that some signals from taste receptor proteins binding with sugars and some L-amino acids converge somewhere along the gustatory neuraxis. However, the results of these experiments also imply that sweet-tasting L-amino acids may possess qualitative taste characteristics that are distinguishable from the prototypical sweetener sucrose.

In spite of its common use as a standard stimulus in peripheral nerve recordings, relatively little is known about the psychophysics of NH-sub-4Cl taste. Rats' detection threshold for this salt was tested under a variety of conditions, including amiloride (100 muM) treatment and bilateral chorda tympani (CT) nerve transection. Detectability was measured with a 2-lever operant discrimination procedure used previously to measure detection thresholds for NaCl and KCl. Although NH-sub-4Cl and KCl appear to share a common taste quality and transduction mechanism, the logistic function and threshold for NH-sub-4Cl were found to be more similar to those of NaCl than to those of KCl. Like that of KCl, however, the detection threshold for NH4Cl increased significantly with CT transection (0.54 log-sub-1-sub-0 units, p < .004), but not with amiloride adulteration. This finding supports the hypothesis that the CT is necessary for normal salt detection regardless of stimulus, and suggests that amiloride does not appreciably impact responses to nonsodium salts at the behavioral level., (((c) 2007 APA, all rights reserved).)

Current evidence suggests salt taste transduction involves at least two mechanisms, one that is amiloride sensitive and appears to use apically located epithelial sodium channels relatively selective for Na(+) and a second that is amiloride insensitive and uses a variant of the transient receptor potential vanilloid receptor 1 (TRPV1) that serves as a nonspecific cation channel. To provide a functional context for these findings, we trained Trpv1 knockout (KO) and wild-type (WT) C57BL/6J mice (n = 9 or 10/group) in a two-response operant discrimination procedure and measured detection thresholds to NaCl and KCl with and without amiloride. The KO and WT mice had similar detection thresholds for NaCl and KCl. Amiloride shifted the NaCl sensitivity curve to the same degree in both groups and had virtually no effect on KCl thresholds. In addition, a more detailed analysis of chorda tympani nerve (CT) responses to NaCl, with and without benzamil (Bz, an amiloride analog) treatment revealed that the tonic portion of the CT response of KO mice to NaCl + Bz was absent, but both KO and WT mice displayed some degree of a phasic response to NaCl with and without Bz. Because these transients constitute the entire CT response to NaCl + Bz in Trpv1 KO mice, it is possible that these signals are sufficient to maintain normal NaCl detectabilty in the behavioral task used here. Additionally, there may be other amiloride-insensitive salt transduction mechanisms in taste receptor fields other than the anterior tongue that maintain normal salt detection performance in the KO mice.

Chorda tympani nerve (CT) transection in rats severely impairs NaCl taste detection. These rats can detect higher concentrations of NaCl, however, suggesting that remaining oral nerves maintain some salt sensibility. Rats were tested in a gustometer with a 2-response operant taste-detection task before and after sham surgery (n = 5), combined transection of the CT and the greater superficial petrosal nerves (GSP; 7x, n = 6), or transection of the glossopharyngeal nerve (GL; 9x, n = 4). Thresholds did not significantly change after sham surgery. Although the GL responds to NaCl and innervates nearly 60% of total taste buds, 9x surgery had no effect. However, 7x surgery increased NaCl detection threshold by approximately 2.5 log(10) units, greater than that reported for CT transection alone. These results suggest that the GSP contributes to NaCl sensitivity in rats and also demonstrate that the GL and perhaps the superior laryngeal and lingual nerve proper can maintain some NaCl detectability at high concentrations. These findings confirm the primacy of the 7th nerve relative to the 9th nerve in sensibility of NaCl in the rat model., (Copyright 2006 APA, all rights reserved.)

We tested whether MC4R null mice display altered gustatory function relative to wild-type controls that may contribute to the characteristic hyperphagia and obesity associated with this gene deletion. Mice were tested for their licking responses to prototypical taste solutions (sucrose, NaCl, quinine, citric acid) in series of daily 30-min sessions in which a range of concentrations of each tastant was available in randomized blocks of 5-s trials. Notwithstanding some minor deviations, the concentration-response functions of the MC4R null and wild-type mice were basically the same for all of the prototypical compounds tested here. Thus, taste-based appetitive and avoidance behavior is expressed in the absence of the MC4 receptor, demonstrating that this critical component in the melanocortin system is not required for normal affective gustatory function to be maintained.

Using a brief-access taste assay, we show in the present report that although phospholipase C beta2 knockout (PLCbeta2 KO) mice are unresponsive to low- and midrange concentrations of quinine and denatonium, they do significantly avoid licking higher concentrations of these aversive compounds. PLCbeta2 KO mice displayed no concentration-dependent licking of the prototypical sweetener sucrose but were similar to wild-type mice in their responses to citric acid and NaCl, notwithstanding some interesting exceptions. Although these findings confirm an essential role for PLCbeta2 in taste responsiveness to sucrose and to low- to midrange concentrations of quinine and denatonium in mice as previously reported, they importantly suggest that higher concentrations of the latter two compounds, which are bitter to humans, can engage a PLCbeta2-independent taste transduction pathway.

The process by which the mammalian nervous system represents the features of a sapid stimulus that lead to a perception of taste quality has long been controversial. The labeled-line (sparse coding) view differs from the across-neuron pattern (ensemble) counterpoint in proposing that activity in a given class of neurons is necessary and sufficient to generate a specific taste perception. This article critically reviews molecular, electro-physiological, and behavioral findings that bear on the issue. In the peripheral gustatory system, the authors conclude that most qualities appear to be signaled by labeled lines; however, elements of both types of coding characterize signaling of sodium salts. Given the heterogeneity of neuronal tuning functions in the brain, the central coding mechanism is less clear. Both sparse coding and neuronal ensemble models remain viable possibilities. Furthermore, temporal patterns of discharge could contribute additional information. Ultimately, until specific classes of neurons can be selectively manipulated and perceptual consequences assessed, it will be difficult to go beyond mere correlation and conclusively discern the validity of these coding models.

Using a lickometer, we assessed the effect of drinking spout orifice size on the licking behavior of inbred mice [C57BL/6J, SWR/J, 129P3/J and DBA/2J]. Animals licked from drinking spout sipper tubes that had what were defined as either a large (2.7 mm) or a small (1.5 mm) orifice. Mice took approximately twice as many licks from a stationary single small orifice drinking spout than when licking from a spout with a large orifice during separate 30-min sessions. However, their total intake volume was approximately the same. We calculated that mice received a mean of 0.55 muL per lick from the drinking tubes with a small orifice and a mean of 1.15 muL per lick from the drinking tubes with a large orifice. Thus, the animals appear to have regulated their fluid intake by proportionally adjusting their licking as a function of the lick volume. On average, this regulation occurred through modulation of the size of licking bursts and not their frequency. However, strain differences in compensation strategy were observed. When licking was restricted to a series of 5-s trials in a 30-min brief access test session, the smaller orifice size increased the range of responsiveness that was expressed. Mice increased their average licks per trial by 20% and took 60% more trials when licking from a spout with a small orifice. Interestingly, when the orifice size was quasi-randomly varied within a brief access session, licking was greater from large orifice drinking spouts, suggesting that water delivered from the two orifice sizes differs in its reinforcement efficacy. These findings demonstrate that drinking spout orifice size can significantly influence experimental outcomes in licking tests involving mice and care should be taken in controlling this variable in testing the effects of taste or other factors on ingestive behavior.

We examined the necessity of alpha-gustducin, a G protein alpha-subunit expressed in taste cells, to taste-mediated licking responses of mice to sapid stimuli. To this end, we measured licking responses of alpha-gustducin knock-out (Gus-/-) mice and heterozygotic littermate controls (Gus+/-) to a variety of 'bitter', 'umami', 'sweet', 'salty' and 'sour' taste stimuli. All previous studies of how Gus-/- mice ingest taste stimuli have used long-term (i.e. 48 h) preference tests, which may be confounded by post-ingestive and/or experiential effects of the taste stimuli. We minimized these confounds by using a brief-access taste test, which quantifies immediate lick responses to extremely small volumes of sapid solutions. We found that deleting alpha-gustducin (i) dramatically reduced the aversiveness of a diverse range of 'bitter' taste stimuli; (ii) moderately decreased appetitive licking to low and intermediate concentrations of an 'umami' taste stimulus (monosodium glutamate in the presence of 100 microM amiloride), but virtually eliminated the normal aversion to high concentrations of the same taste stimulus; (iii) slightly decreased appetitive licking to 'sweet' taste stimuli; and (iv) modestly reduced the aversiveness of high, but not low or intermediate, concentrations of NaCl. There was no significant effect of deleting alpha-gustducin on licking responses to NH4Cl or HCl.

The amiloride-sensitive salt transduction pathway is thought to be critical for the discrimination between sodium and nonsodium salts in rodents. In rats, lingual application of amiloride appears to render NaCl qualitatively indistinguishable from KCl. In this study, we tested four strains of mice for salt discriminability. In one strain (C57BL/6J), chorda tympani nerve (CT) responses to NaCl are attenuated by amiloride, and in the other three strains (BALB/cByJ, 129P3/J, DBA/2J) they are not. Under water-restriction conditions, these mice (7 mice/strain) were trained in a gustometer to lick for water from one reinforcement spout in response to a five-lick presentation of NaCl and to lick from another in response to KCl [salt concentration was varied (0.1-1 M) to render intensity irrelevant]. Mice were then tested with the stimuli dissolved in amiloride hydrochloride, and the latter was used as the reinforcer as well. Each concentration of amiloride (0.1-100 microM) was used on 2 separate days with control sessions interposed. Mice from all four strains were able to discriminate NaCl from KCl reliably. Amiloride impaired this discrimination in a dose-dependent fashion. Moreover, performance on NaCl trials appeared to be more affected by amiloride than that on KCl trials in all four strains. Thus, in contrast to the predictions based on CT recordings, discrimination in all four strains appeared to depend on the amiloride-sensitive transduction pathway, which, in the case of BALB/cByJ, 129P3/J, and DBA/2J (and perhaps C57BL/6 as well), may exist in taste buds innervated by nerves other than the CT.

In rats, chorda tympani nerve transection (CTX) greatly increases the detection threshold of sodium chloride (NaCl) and severely disrupts salt discriminability. Here it is shown that CTX has surprisingly little effect, if any, on suprathreshold intensity discrimination. Glossopharyngeal nerve transection (GLX), which has no reported effect on salt sensibility, also did not affect performance. Rats were tested in a 2-response, operant taste intensity discrimination task. Difference thresholds for CTX rats were only slightly higher (-0.15 log/10 unit) than those for GLX and sham-transected rats, when 0.05 M served as the standard, and did not significantly differ when 0.1 M NaCl was the standard. Although the perceived intensity of NaCl might be reduced by CTX, input from remaining taste nerves sufficiently maintains the relative discriminability of suprathreshold NaCl concentrations.

The concentration-dependent decrease in quinine licking by rats is substantially attenuated by combined bilateral transection of the chorda tympani (CT) and glossopharyngeal (GL) nerves, but transection of either nerve alone produces marginal impairments at most. Here we tested whether regeneration of one or both of these nerves after combined transection would result in recovery of taste avoidance. Water-restricted rats were presented with a series of brief-access (5 s) taste trials (water and 0.003-3.0 mM quinine-HCl) in a 5-day test block of 40-min sessions both before nerve transection and starting 75-77 days after transection. Licking avoidance returned to presurgical levels when both nerves were allowed to regenerate. When only the GL was allowed to regenerate, performance did not differ from that of sham-transected animals. This suggests that even after considerable gustatory deafferentation, regeneration has the capacity to restore normal taste-guided behavior. Surprisingly, when only the CT was allowed to regenerate, avoidance behavior was severely impaired and was not different from that of rats in which regeneration of both nerves was prevented. Taking into account prior findings, it appears that the absence of the GL in the presence of an intact CT is fundamentally different from the absence of the GL in the presence of a regenerated CT with respect to some taste functions. This represents the first reported instance to our knowledge in which the capacity of a regenerated nerve to maintain taste-guided behavior was distinctly different from that of an intact nerve in a rodent model., (Copyright 2004 American Physiological Society)