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）：嗅觉系统为遗传定义的神经元电路如何产生正常的大脑功能提供了独特的窗口。挥发性气味是 由大型嗅觉受体基因检测到，每个基因都由大脑的特定功能输入表示。在鉴定出对气味感知显着贡献的主要嗅觉受体基因方面的困难，阻碍了理解哺乳动物嗅觉的进展。该建议介绍了小型主嗅觉受体家族的个别成员，痕量胺相关受体（TAAR）如何有助于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，提出了重要功能。我们提出了遗传学，生理和行为的结合，以检验以下假设：TAAR是一种不同途径中最敏感的受体，它介导了对胺与生物学相关的气味类别的先天厌恶，这些剂量是由衰减和微生物作用产生的。具体目标1是确定TAAR是否有助于将行为检测阈值设置为胺。具体目标2是 确定TAAR输入的选择性激活是否可以驱动厌恶行为。具体目标3是确定将TAAR输入的位置重新映射到嗅球的位置是否改变了气味感知。实现这些目标将提高我们对这种新型化学感应基因家族如何促进嗅觉的理解，以及哺乳动物嗅觉电路的组织如何影响包括人类在内的哺乳动物中的气味感知。