T1R-Independent Oronasal Detection of Carbohydrates in the Mouse Model: A Psychophysical Analysis

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Title: T1R-Independent Oronasal Detection of Carbohydrates in the Mouse Model: A Psychophysical Analysis
Authors: N/A
Committee Members: Hamel, Elizabeth (author); Spector, Alan C. (professor directing dissertation); Roper, Michael Gabriel (university representative); Dewan, Adam Kabir (committee member); Ganley, Colleen M. (committee member); Vincis, Roberto (committee member); Florida State University (degree granting institution); College of Arts and Sciences (degree granting college); Department of Psychology (degree granting department)
Summary: It is uncontested that one key role of taste is to allow animals to detect food-derived chemicals and distinguish between beneficial nutrients and harmful toxins. In humans and many mammals, there are thought to be 5 basic taste qualities: sour, salty, umami, bitter, and sweet. "Sweet" is the adjective used by humans to describe the perceptual quality of sugars and non-caloric sweeteners. Sugars are one form of carbohydrates that make up an important portion of any diet. Other dietary carbohydrates include oligosaccharides and polysaccharides. Orosensory detection of carbohydrates is beneficial, as glucose is a crucial source of energy and required for normal brain function. Sugars interact with the T1R2 + T1R3 heterodimeric receptor found in taste receptor cells. There is evidence that strongly suggests the presence of T1R-independent mechanisms that contribute to carbohydrate detection for glucose and glucose polymers, but such processes remain to be fully understood. It has been shown that rodents avidly consume maltodextrins, or oligosaccharide mixtures, in short-term, long-term, and brief-access tests. Oligosaccharides appear to generate a qualitative perception distinct from the basic tastes, like sweet. Mice lacking one or both subunits of the T1R2 + T1R3 still display relatively normal preference for maltodextrins, yet have blunted responsiveness to sugars. In Chapter 2, we tested whether taste contributes to maltodextrin responsiveness. Mice with (WT) and without a functional T1R3 subunit (KO), underwent sham (SHAM) or lingual gustatory nerve transection (NX). Following surgery, mice were tested, after a ~23-h fast, on their concentration-dependent licking responses to Maltrin, a maltodextrin, and sucrose in a brief-access paradigm (10-s access trials, 30-min sessions), which minimizes postingestive influence on responsiveness. NX mice displayed significantly blunted lick responses and initiated fewer trials to Maltrin. The SHAM mice displayed similar responses to Maltrin across sessions, albeit KO-SHAM displayed lower lick responses at higher concentrations in the first session. The KO mice exhibited some concentration-dependent licking to sucrose, though attenuated. This could be due to prior exposure to Maltrin, and learning associated with postingestive cues. However, NX blunted this responsiveness in both WT and KO mice; in the KO-NX group severely so. The results suggest an intact chorda tympani and/or glossopharyngeal nerve are required for normal concentration-dependent licking to maltodextrin and sucrose solutions confirming a contribution of gustatory signals to the behavior. In Chapter 3, we explored the potential for a T1R-independent pathway to contribute to the taste detection of glucose. One proposed mechanism, the sodium glucose cotransporter-1 (SGLT1), has been found to be expressed in T1R3-positive taste receptor cells. This transporter is thought to primarily play a role in glucose absorption from the intestine and glucose-sensing in metabolic signaling pathways but may also contribute to T1R-independent signaling of the oral presence of glucose. Prior studies of peripheral gustatory nerve responsiveness in mice, or psychophysical assessment of detection thresholds in humans, suggest the addition of small amounts of NaCl to the solution enhance the glucose signal; an effect reversed by oral treatment with the SGLT inhibitor, phlorizin. To further investigate this phenomenon, WT and T1R3KO were trained on a two-response operant task to differentially respond to 2 M glucose + 0.01 M NaCl vs. 0.01 M NaCl in a gustometer. Despite extensive training T1R3KO mice could not perform the task reliably. WT mice were then tested on a descending array of concentrations of glucose + 0.01 M NaCl, followed by glucose without NaCl. Interestingly, the WT mice exhibited a slightly lower, though significant, detection threshold to glucose alone, which could be attributed to experience. These results provided no psychophysical evidence of a non-T1R taste pathway involved in the detection of glucose in mice, though it is possible SGLT1 contributes to taste functions other than sensory discriminative detection. The final experiment (Chapter 4) explored the potential for sensory signals outside of the gustatory system to contribute to carbohydrate detection. The literature has examples of rodents using odor cues of tastants to guide responsiveness. Here, we assessed the olfactory sensitivity of head-fixed WT and T1R3KO mice in a Go/No-Go conditioning procedure to different carbohydrate stimuli. WT mice could detect the volatiles associated with Maltrin and glucose stimuli in a concentration-dependent manner. Because of their limited volatility at room temperature, it is unlikely the carbohydrates are being detected by mice, rather it is probably contaminants within the solution guiding responsiveness. T1R3KO mice could similarly detect these glucose-associated odors but were apparently unable to use such cues to guide their performance in the gustometer (Chapter 3). Olfactory detection thresholds to these stimuli are lower than those of taste.
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Abstract:It is uncontested that one key role of taste is to allow animals to detect food-derived chemicals and distinguish between beneficial nutrients and harmful toxins. In humans and many mammals, there are thought to be 5 basic taste qualities: sour, salty, umami, bitter, and sweet. "Sweet" is the adjective used by humans to describe the perceptual quality of sugars and non-caloric sweeteners. Sugars are one form of carbohydrates that make up an important portion of any diet. Other dietary carbohydrates include oligosaccharides and polysaccharides. Orosensory detection of carbohydrates is beneficial, as glucose is a crucial source of energy and required for normal brain function. Sugars interact with the T1R2 + T1R3 heterodimeric receptor found in taste receptor cells. There is evidence that strongly suggests the presence of T1R-independent mechanisms that contribute to carbohydrate detection for glucose and glucose polymers, but such processes remain to be fully understood. It has been shown that rodents avidly consume maltodextrins, or oligosaccharide mixtures, in short-term, long-term, and brief-access tests. Oligosaccharides appear to generate a qualitative perception distinct from the basic tastes, like sweet. Mice lacking one or both subunits of the T1R2 + T1R3 still display relatively normal preference for maltodextrins, yet have blunted responsiveness to sugars. In Chapter 2, we tested whether taste contributes to maltodextrin responsiveness. Mice with (WT) and without a functional T1R3 subunit (KO), underwent sham (SHAM) or lingual gustatory nerve transection (NX). Following surgery, mice were tested, after a ~23-h fast, on their concentration-dependent licking responses to Maltrin, a maltodextrin, and sucrose in a brief-access paradigm (10-s access trials, 30-min sessions), which minimizes postingestive influence on responsiveness. NX mice displayed significantly blunted lick responses and initiated fewer trials to Maltrin. The SHAM mice displayed similar responses to Maltrin across sessions, albeit KO-SHAM displayed lower lick responses at higher concentrations in the first session. The KO mice exhibited some concentration-dependent licking to sucrose, though attenuated. This could be due to prior exposure to Maltrin, and learning associated with postingestive cues. However, NX blunted this responsiveness in both WT and KO mice; in the KO-NX group severely so. The results suggest an intact chorda tympani and/or glossopharyngeal nerve are required for normal concentration-dependent licking to maltodextrin and sucrose solutions confirming a contribution of gustatory signals to the behavior. In Chapter 3, we explored the potential for a T1R-independent pathway to contribute to the taste detection of glucose. One proposed mechanism, the sodium glucose cotransporter-1 (SGLT1), has been found to be expressed in T1R3-positive taste receptor cells. This transporter is thought to primarily play a role in glucose absorption from the intestine and glucose-sensing in metabolic signaling pathways but may also contribute to T1R-independent signaling of the oral presence of glucose. Prior studies of peripheral gustatory nerve responsiveness in mice, or psychophysical assessment of detection thresholds in humans, suggest the addition of small amounts of NaCl to the solution enhance the glucose signal; an effect reversed by oral treatment with the SGLT inhibitor, phlorizin. To further investigate this phenomenon, WT and T1R3KO were trained on a two-response operant task to differentially respond to 2 M glucose + 0.01 M NaCl vs. 0.01 M NaCl in a gustometer. Despite extensive training T1R3KO mice could not perform the task reliably. WT mice were then tested on a descending array of concentrations of glucose + 0.01 M NaCl, followed by glucose without NaCl. Interestingly, the WT mice exhibited a slightly lower, though significant, detection threshold to glucose alone, which could be attributed to experience. These results provided no psychophysical evidence of a non-T1R taste pathway involved in the detection of glucose in mice, though it is possible SGLT1 contributes to taste functions other than sensory discriminative detection. The final experiment (Chapter 4) explored the potential for sensory signals outside of the gustatory system to contribute to carbohydrate detection. The literature has examples of rodents using odor cues of tastants to guide responsiveness. Here, we assessed the olfactory sensitivity of head-fixed WT and T1R3KO mice in a Go/No-Go conditioning procedure to different carbohydrate stimuli. WT mice could detect the volatiles associated with Maltrin and glucose stimuli in a concentration-dependent manner. Because of their limited volatility at room temperature, it is unlikely the carbohydrates are being detected by mice, rather it is probably contaminants within the solution guiding responsiveness. T1R3KO mice could similarly detect these glucose-associated odors but were apparently unable to use such cues to guide their performance in the gustometer (Chapter 3). Olfactory detection thresholds to these stimuli are lower than those of taste.