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，了解遗传定义的神经元回路如何产生正常的大脑功能。挥发性气味剂是 由一个大家族的嗅觉受体基因检测，其中每一个都代表了大脑的特定功能输入。在识别对气味感知有重要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。该提案解决了一个小的主要嗅觉受体家族，微量胺相关受体（TAAR）的个体成员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是保守的，表明其具有重要功能。我们提出了一个遗传学，生理学和行为相结合的假设，TAAR是最敏感的受体在一个独特的途径，介导先天厌恶胺-生物相关类的气味产生的腐烂和微生物的行动。具体目标1是确定TAAR是否显著有助于设置胺的行为检测阈值。具体目标二是 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是否会改变气味感知。实现这些目标将促进我们对这种新的化学感受基因家族如何促进嗅觉的理解，以及哺乳动物嗅觉回路的组织如何影响哺乳动物（包括人类）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.