Trace Amine-Associated Receptors and Olfactory Behavior in Mammals

描述(由申请人提供)：嗅觉系统提供了一个独特的窗口，可以了解基因定义的神经元电路如何产生正常的大脑功能。挥发性气味是 由嗅觉受体基因大家族检测，每个基因都代表大脑的特定功能输入。在识别对气味知觉有重大贡献的主要嗅觉受体基因方面的困难阻碍了对哺乳动物嗅觉的理解的进展。这项建议阐述了一个小型主要嗅觉受体家族的个体成员--痕量胺相关受体(TAAR)--如何对哺乳动物的气味感知做出贡献。TAAR在人类、小鼠和其他脊椎动物中都是保守的，这表明它具有重要的功能。我们建议结合遗传学、生理学和行为学来检验这样一个假设，即TAAR是一条独特的途径中最敏感的受体，该途径介导了对胺的先天厌恶--胺是一类由腐烂和微生物作用产生的生物相关气味。具体目标1是确定TAAR是否对设置胺的行为检测阈值有重大贡献。具体目标2是 确定选择性激活TAAR输入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是否会改变气味感知。实现这些目标将促进我们理解这个新的化学感觉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。

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.