Psychophysical Evaluation of Taste Function

描述（由申请人提供）：味觉与摄食后生理学相互作用以控制进食和饮水行为是无可争议的，因此可以得出结论，味觉过程的异常可能影响涉及营养状态、水矿物质平衡和肥胖的更复杂的临床疾病。因此，动物模型的发展，其中味觉系统可以实验操纵，是必不可少的获得正常和异常味觉功能的基础神经生物学的理解。对任何非人类动物的感觉和知觉进行心理物理学评估都是具有挑战性的，但这是旨在理解感觉功能神经生物学的整体分析策略的绝对必要组成部分。没有这些知识，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。所提出的实验的总体目标是使用严格的心理物理学方法来评估G蛋白偶联味觉受体的T1 R家族的个体成员对正常味觉感知的必要性。T1 R1和T1 R3亚基联合收割机在味觉受体细胞中形成与L-氨基酸结合的异聚体，T1 R2和T1 R3亚基联合收割机形成与糖、人工甜味剂和D-氨基酸亚类结合的异聚体。虽然基因敲除（KO）小鼠，有各种T1 R亚基基因删除似乎缺乏相应的配体的味觉反应，现有的数据是严重限制的功能范围，有理由相信，这些动物可能不会完全aguesic相应的化合物。事实上，关于野生型（WT）小鼠中糖和L-氨基酸的感知特征仍存在许多问题。使用WT、T1 R1、T1 R2、T1 R3和T1 R2 +3 KO小鼠，我们将评估每个T1 R亚基对于原型T1 R配体的1）味觉检测和2）味觉辨别的相对必要性，并检验这些KO小鼠中存在残余味觉功能的假设。使用基于操作性的味觉概括任务，我们还将确定可检测到的T1 R配体的定性特征，从而构建WT和KO动物的感知图。这些实验将从精神病学的角度定义一类重要的味觉受体对小鼠模型中正常味觉功能的贡献，该模型正被广泛用于哺乳动物化学感觉过程的研究。

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.