Psychophysical Evaluation of Taste Function

描述(由申请人提供)：毫无疑问，味觉与消化后生理相互作用，控制进食和饮酒行为，因此，味觉过程的异常可能会影响更复杂的临床疾病，涉及营养状态、水矿物质平衡和肥胖。因此，发展动物模型，其中味觉系统可以进行实验操作，对于了解正常和异常味觉功能的潜在神经生物学是必不可少的。对任何非人类动物的感觉和知觉进行心理物理评估是具有挑战性的，但对于旨在了解感觉功能的神经生物学的整体分析策略来说，这是一个绝对必要的组成部分。如果没有这样的知识，就不可能将感觉系统的生理学和分子生物学与最终的功能结果--行为联系起来。拟议实验的总体目标是使用严格的心理物理方法来评估G蛋白偶联味觉受体T1R家族的个体成员对正常味觉的必要性。在味觉感受器细胞中，T1R1和T1R3亚基结合形成异构体，与L氨基酸结合，T1R2和T1R3亚基结合形成异构体，与糖、人造甜味剂和D-氨基酸的一部分结合。尽管基因缺失了各种T1R亚基的基因敲除(KO)小鼠似乎对相应的配体缺乏味觉反应，但现有的数据在功能范围上严重受限，有理由相信这些动物可能对各自的化合物并不完全过敏。事实上，关于糖和L氨基酸在野生型(WT)小鼠中的感知特征仍然存在许多问题。使用WT、T1R1、T1R2、T1R3和T1R2+3KO小鼠，我们将评估每个T1R亚基对1)味觉检测和2)典型T1R配体的味道辨别的相对必要性，并检验这些KO小鼠存在剩余味觉功能的假设。使用基于操作的味觉概括任务，我们还将确定那些可检测到的T1R配体的质量特征，从而构建WT和KO动物的知觉图谱。这些实验将从心理物理上确定一类重要的味觉受体在小鼠模型中对正常味觉功能的贡献，该模型正被广泛用于研究哺乳动物的化学感觉过程。

DESCRIPTION (provided by applicant): 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.