It is uncontested that taste interacts with postingestive physiology to control feeding and drinking behavior, and thus it follows that abnormalities in gustatory processes likely influence more complex clinical disorders nvolving nutritional status, hydromineral balance, and obesity. Accordingly, the development of animal models, in which the gustatory system can be experimentally manipulated, is essential to gain an understanding of the underlying neurobiology of normal and abnormal taste function. The psychophysical assessment of sensation and perception in any nonhuman animal is challenging, but an absolutely necessary component to the overall analytical strategy aimed at understanding the neurobiology of sensory function. Without such knowledge, it is impossible to link the physiology and molecular biology of the sensory system to the ultimate functional outcome - behavior. The overall aim of the proposed experiments is to use rigorous psychophysical methodology to assess the necessity of indivdual members of the T1R family of G-protein coupled taste receptors to normal taste perception. The T1R1 and T1R3 subunits combine to form a heteromer in taste receptor cells that binds with L-amino acids, and the T1R2 and T1R3 subunits combine to form a heteromer that binds with sugars, artificial sweetners and a subset of D-amino acids. Although knock-out (KO) mice that have had various T1R subunits genetically deleted appear to lack taste responsiveness to the corresponding ligands, the existing body of data is severely limited in functional scope, and there is reason to believe that these animals may not be entirely aguesic to the respective compounds. Indeed, many questions remain regarding the perceptual characteristics of sugars and L-amino acids in wild type (WT) mice. Using WT, T1R1 , T1R2, T1R3, and T1R2+3 KO mice, we will assess the relative necessity of each T1R subunit for 1) taste detection and 2) taste discrimination of prototypical T1R ligands and test the hypothesis that residual taste function is present in these KO mice. Using an operantly based taste generalization task, we will also determine the qualitative characteristics of those T1R ligands that are detectable and thus construct a perceptual map for WT and KO animals. These experiments will psychophysically define the contribution of an important class of taste receptors to normal gustatory function in the mouse model, which is becoming widely adopted for study of mammalian chemosensory processes. ? ? ?
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