Psychophysical Evaluation of Taste Function

味觉功能的心理物理学评估

• 批准号: 7247109
• 负责人: Alan C Spector
• 金额: $ 25.43万
• 依托单位: FLORIDA STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-12-15 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7247109
• 关键词: Address; Adopted; Affect; Alkaloids; American; Amino Acids; Animal Model; Animals; Artificial Sweeteners; Attention; Behavior; Binding; Binding Sites; Characteristics; Chemicals; Class; Clinical; Complex; Country; Coupled; Data; Detection; Development; Discrimination; Disease; Employee Strikes; Epidemic; Equilibrium; Esthesia; Evaluation; Family; Funding; G-Protein-Coupled Receptors; GTP-Binding Proteins; Gene Deletion; Genetically Engineered Mouse; Goals; Knock-out; Knockout Mice; Knowledge; Ligands; Link; Maps; Methodology; Modeling; Molecular Biology; Molecular Genetics; Mus; Neurobiology; Nutritional status; Obesity; Perception; Physiology; Procedures; Process; Proteins; Psychophysiology; Rattus; Receptor Cell; Relative (related person); Research; Research Personnel; Residual state; Sensory; System; Taste Perception; Techniques; Testing; Thinking; Time; Wild Type Mouse; Work; analog; base; defined contribution; drinking behavior; feeding; functional outcomes; insight; member; mouse model; receptor; research study; sensory system; sugar

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.

描述（由申请人提供）：毫无争议的是，味觉与食后生理学相互作用以控制进食和饮水行为，因此味觉过程的异常可能会影响涉及营养状况、水矿物质平衡和肥胖的更复杂的临床疾病。因此，开发可以通过实验操纵味觉系统的动物模型对于了解正常和异常味觉功能的潜在神经生物学至关重要。对任何非人类动物的感觉和知觉进行心理物理学评估都具有挑战性，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，这是绝对必要的组成部分。如果没有这些知识，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。拟议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 T1R 家族个体成员对正常味觉感知的必要性。 T1R1 和 T1R3 亚基在味觉受体细胞中结合形成异聚体，与 L-氨基酸结合，T1R2 和 T1R3 亚基结合形成异聚体，与糖、人造甜味剂和 D-氨基酸子集结合。尽管基因删除了各种T1R亚基的敲除（KO）小鼠似乎缺乏对相应配体的味觉反应，但现有的数据在功能范围上受到严重限制，并且有理由相信这些动物可能不对各自的化合物完全无水。事实上，关于野生型 (WT) 小鼠中糖和 L-氨基酸的感知特征仍然存在许多问题。使用 WT、T1R1、T1R2、T1R3 和 T1R2+3 KO 小鼠，我们将评估每个 T1R 亚基对于 1) 味觉检测和 2) 原型 T1R 配体的味觉辨别的相对必要性，并测试残留味觉功能存在的假设在这些 KO 小鼠中。使用基于操作的味觉泛化任务，我们还将确定那些可检测的 T1R 配体的定性特征，从而构建 WT 和 KO 动物的感知图。这些实验将从心理物理学上定义一类重要的味觉受体对小鼠模型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。