Despite the importance of complex carbohydrates and amino acids in the diet of omnivores including humans, our understanding of the peripheral and central mechanisms underlying the detection and processing of these critical dietary compounds by the gustatory system remains in its infancy. Since the initial discovery and characterization of the T1R family of receptor proteins, evidence has accumulated supporting the T1R2+3 heterodimer as the primary taste receptor for sweet-tasting ligands. Likewise, the T1R1+3 heterodimer has been suggested to be critical in the perception of the prototypical umami compound, L-glutamate, when in the presence of the 5'-ribonucleotide, inosine monophosphate (IMP). At the same time, however, research from this lab and others has suggested that additional, potentially T1R-independent receptors may be involved in signaling the presence of at least some amino acids, including L-glutamate when mixed with IMP. Such conclusions are based, in part, on residual behavioral and neural responsiveness in single knock-out (KO) mice missing either T1R1 or T1R3. Similarly, mice lacking either T1R2 or T1R3, while displaying severely impaired psychophysical responsiveness to common sugars are only mildly impaired in responsiveness to glucose polymer mixtures such as Polycose. The taste function spared following deletion of single T1R subunits of the heterodimers may be due to the ability of the remaining subunit to form a homodimer or combine with an unidentified protein to serve as a partially effective receptor. Alternatively, such maintained function could reflect T1R-independent mechanisms. Accordingly, with the use of rigorous psychophysical methodology, T1R2+3 double KO and newly generated T1R1+3 double KO mice along with wild type (WT) mice will tested in the proposed studies to determine whether T1R-independent receptors contribute to the detectability of glucose polymer solutions and select amino acids such as L-glutamate (+IMP), glycine, and L-lysine. Nerve transection studies will isolate the critical oral receptor field(s) responsible for the maintained behavioral responsiveness to the relevant stimuli in the double KO mice. Finally, because it is possible that any lack of behavioral competence in a given taste task does not reflect the absence of a peripheral signal reaching the brain, single-unit recording in the rostral nucleus of the solitary tract (rNST), the first central taste relay, f WT and double KO mice will be performed. This will determine whether signals generated from these taste stimuli reach the brain and from what oral field they originate. Moreover, whether the loss of the relevant T1R heterodimeric receptors differentially affects evoked activity in particulr functional neuronal types, as defined by response profile and anatomical projection status, will be determined. These integrated behavioral and electrophysiological studies will not only reveal whether T1R-independent taste signals for glucose polymers and select amino acids exist, but will provide insight into their neural channeling and their functional significance.
A variety of nutritional and metabolic disorders including obesity, anorexia, and diabetes, as well as hypertension and cardiovascular disease are caused or exacerbated by ingestive behavior. Given that taste plays a large role in food selection and caloric intake, gaining a better understanding of how complex carbohydrates and amino acids, two critical components of the diet, are detected and processed by the gustatory system should contribute to interventions that can lead to healthier feeding and more favorable metabolic and nutritional outcomes.
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