Trace Amine-Associated Receptors and Olfactory Behavior in Mammals

哺乳动物中的痕量胺相关受体和嗅觉行为

• 批准号: 8761820
• 负责人: Thomas Bozza
• 金额: $ 53.63万
• 依托单位: NORTHWESTERN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-07-15 至 2019-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8761820
• 关键词: Address; Afferent Neurons; Amines; Behavior; Behavioral; Brain; Chemicals; Data; Detection; Dorsal; Family; G-Protein-Coupled Receptors; Gene Cluster; Gene Family; Genetic; Goals; Health; Human; Individual; Knock-out; Laboratories; Lateral; Learning; Ligands; Light; Location; Mammals; Maps; Measurable; Mediating; Modeling; Mus; Neurons; Odorant Receptors; Odors; Olfactory Pathways; Pathway interactions; Perception; Phenethylamines; Physiology; Quality of life; Receptor Gene; Relative (related person); Reporting; Role; Smell Perception; Source; System; Testing; Vertebrates; Work; defined contribution; experience; food quality; member; microbial; novel; olfactory bulb; olfactory receptor; public health relevance; receptor; receptor sensitivity; research study; response; social; trimethylamine

DESCRIPTION (provided by applicant): The olfactory system provides a unique window into how genetically defined neuronal circuits give rise to normal brain function. Volatile odorants are detected by a large family of olfactory receptor genes, each of which is represented by a specific functional input to the brain. Progress towards understanding mammalian olfaction has been hindered by difficulties in identifying main olfactory receptor genes that contribute significantly to odor perception. This proposal addresses how individual members of a small main olfactory receptor family, the Trace Amine-Associated Receptors (TAARs), contribute to odor perception in mammals. The TAARs are conserved in humans, mice and other vertebrates suggesting an important function. We propose a combination of genetics, physiology and behavior to test the hypothesis that the TAARs are the most sensitive receptors in a distinct pathway that mediates innate aversion to amines-a biologically relevant class of odorants that are produced by decay and microbial action. Specific Aim 1 is to determine whether the TAARs contribute significantly to setting behavioral detection thresholds to amines. Specific Aim 2 is to determine whether selective activation of TAAR inputs can drive aversive behaviors. Specific Aim 3 is to determine whether remapping the location of TAAR inputs to the olfactory bulb alters odor perception. Achieving these aims will advance our understanding of how this novel chemosensory gene family contributes to olfaction, and how the organization of mammalian olfactory circuits influences odor perception in mammals, including humans.

描述（由申请人提供）：嗅觉系统提供了一个独特的窗口，了解基因定义的神经元回路如何产生正常的大脑功能。挥发性气味物质是 由嗅觉受体基因一大家族检测到，每个基因都代表大脑的特定功能输入。由于难以识别对气味感知有显着贡献的主要嗅觉受体基因，理解哺乳动物嗅觉的进展受到阻碍。该提案探讨了主要嗅觉受体家族微量胺相关受体（TAAR）的各个成员如何影响哺乳动物的气味感知。 TAAR 在人类、小鼠和其他脊椎动物中保守，表明其具有重要功能。我们提出了遗传学、生理学和行为学的结合来检验这一假设，即 TAAR 是介导对胺的先天厌恶的独特途径中最敏感的受体，胺是一种由腐烂和微生物作用产生的生物学相关的气味剂。具体目标 1 是确定 TAAR 是否对设置胺的行为检测阈值有显着贡献。具体目标 2 是 确定 TAAR 输入的选择性激活是否会导致厌恶行为。具体目标 3 是确定将 TAAR 输入位置重新映射到嗅球是否会改变气味感知。实现这些目标将加深我们对这种新型化学感应基因家族如何促进嗅觉，以及哺乳动物嗅觉回路的组织如何影响包括人类在内的哺乳动物的气味感知的理解。