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.

After Roux-en-Y gastric bypass surgery (RYGB), patients report consuming fewer fatty and dessert-like foods, and rats display blunted sugar and fat preferences. Here we used a progressive ratio task (PR) 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 1.0 M 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.

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. W ith its primary receptors situated at the front end of the alimentary tract, the gustatory system is integrally involved in guiding food selection, promoting and discouraging intake, and evoking preparatory physiological reflexes (1). To best serve these functions, taste signals must confer with both the contemporary physiological milieu (e.g., satiety, malaise) and neurally stored representations of the associated effects of that particular taste stimulus [e.g., associative history with visceral malaise, as in conditioned taste aversion (CTA)]. However, the neural circuits underlying these critical integrative processes remain to be fully elucidated. In this regard, gustatory cortex (GC), an assemblage of taste-responsive neurons in the anterior dysgranular and agranular layers of insular cortex, is of particular interest (2-7). Receiving convergent input from both the thalamic and limbic taste pathways, GC consists of neurons that may potentially respond to various features of the taste stimulus, including chemosensory and hedonic alike, situated in close proximity to one another (5,(8)(9)(10)(11)(12)(13). Additionally, viscerosensory signals are received in the adjoining region of granular insular cortex (GI) just dorsal and posterior to GC (5,6,11,14). Extensive and reciprocating projections are found both within the subdivisions of G...

Mathes CM, Letourneau C, Blonde GD, le Roux CW, Spector AC. Roux-en-Y gastric bypass in rats progressively decreases the proportion of fat calories selected from a palatable cafeteria diet. Am J Physiol Regul Integr Comp Physiol 310: R952-R959, 2016. First published February 10, 2016 doi:10.1152/ajpregu.00444.2015.-Roux-en-Y gastric bypass surgery (RYGB) decreases caloric intake in both human patients and rodent models. In long-term intake tests, rats decrease their preference for fat and/or sugar after RYGB, and patients may have similar changes in food selection. Here we evaluated the impact of RYGB on intake during a "cafeteria"-style presentation of foods to assess if rats would lower the percentage of calories taken from fat and/or sugar after RYGB in a more complex dietary context. Male Sprague-Dawley rats that underwent either RYGB or sham surgery (Sham) were presurgically and postsurgically given 8-days free access to four semisolid foods representative of different fat and sugar levels along with standard chow and water. Compared with Sham rats, RYGB rats took proportionally fewer calories from fat and more calories from carbohydrates; the latter was not attributable to an increase in sugar intake. The proportion of calories taken from protein after RYGB also increased slightly. Importantly, these postsurgical macronutrient caloric intake changes in the RYGB rats were progressive, making it unlikely that the surgery had an immediate impact on the hedonic evaluation of the foods and strongly suggesting that learning is influencing the food choices. Indeed, despite these dietary shifts, RYGB, as well as Sham, rats continued to select the majority of their calories from the high-fat/high-sugar option. Apparently after RYGB, rats can progressively regulate their intake and selection of complex foods to achieve a seemingly healthier macronutrient dietary composition. supermarket diet; bariatric surgery; diet-induced obesity; conditioned avoidance ROUX-EN-Y GASTRIC BYPASS (RYGB) is an effective means by which to reduce excess body weight in the morbidly obese (e.g., 28). While many physiological changes induced by the operation may contribute to weight loss, there is strong evidence that patients eat less and have reduced appetite (e.g., 1, 13, 35). In some studies, RYGB patients report less frequent consumption of high-fat foods, like cheeses and red meats (e.g., 14); sweets, like soda and candy (e.g., 7, 11, 31); and other palatable mixtures of sugar and fat, such as ice cream (e.g., 2, 10, 30). While self-report measures in humans are vulnerable to inaccuracies (e.g., 9, 15, 23, 24, 33; also see 19), these results are mirrored in rat models of RYGB. After RYGB, rats lose body weight, consume fewer overall calories, and show blunted preferences for high-fat laboratory diets, as well as for sucrose solutions, the soybean oil emulsion Intralipid, and dietary supplements like Ensure that are high in fat and sugar (e.g., 3,5,14,16,22,26,27,36,37).Although these data from rodent models of RYGB are compelling, t...

Gustatory cortex (GC) is widely regarded for its integral role in the acquisition and retention of conditioned taste aversions (CTAs) in rodents, but large lesions in this area do not always result in CTA impairment. Recently, using a new lesion mapping system, we found severe CTA expression deficits were associated with damage to a critical zone that included the posterior half of GC in addition to the insular cortex (IC) that is just dorsal and caudal to this region (visceral cortex). Importantly, lesions in anterior GC were without effect. Here, neurotoxic-induced bilateral lesions were placed in the anterior half of this critical damage zone, at the confluence of the posterior GC and the anterior visceral cortex (termed IC2), the posterior half of this critical damage zone that contains just VC (termed IC3), or both of these subregions (IC2+IC3). Then, pre- and post-surgically acquired CTAs (to 0.1M NaCl and 0.1M sucrose, respectively) were assessed postsurgically in 15-min single-bottle and 96-h two-bottle tests. Li-injected rats with histologically-confirmed bilateral lesions in IC2 exhibited the most severe CTA deficits, while those with bilateral lesions in IC3 were relatively normal, exhibiting transient disruptions in the single-bottle sessions. Group-wise lesion maps showed CTA-impaired rats had more extensive damage to IC2 than did unimpaired rats. Some individual differences in CTA expression among individual rats with similar lesion profiles were observed, suggesting idiosyncrasies in the topographical representation of information in IC. Nevertheless, this study implicates IC2 as the critical zone of IC for normal CTA expression.

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 whereas processing of the sensory signals in reward circuits could differ. Utilizing 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 irrespective of its intensity. The rats, grouped by a characteristic bimodal phenotypic difference in their preference for sucralose, treated this artificial sweetener as qualitatively different with the sucralose-preferring rats finding the stimulus much more perceptually similar to sucrose, relative to sucralose-avoiding rats. Although the possibility that stimulus palatability may have served as a discriminative cue cannot entirely be ruled out, the profile of results suggested 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 roughly 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.

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.

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.