Peripheral Odor Coding in Mammals

描述（由申请人提供）：哺乳动物的嗅觉系统已经进化到能够检测和区分无数挥发性气味分子，并对来自食物、毒素、配偶或捕食者的化学信号做出反应，通过利用一个大家族的气味受体（or）蛋白（G蛋白偶联受体的成员）来最大化适应。然而，OR和相应气味剂之间的映射非常复杂：给定的OR可以被多种气味激活，就像一种气味可以激活一组OR一样。大量的受体和气味，加上多对多的映射关系，使得气味- or对的系统识别成为一项艰巨的任务。尽管我们的实验室和其他实验室已经成功地通过异源细胞表达技术将气味映射到受体，但很少有研究在体内验证这些。在这里，我们提出了一种方法来绘制在清醒行为动物中气味刺激激活的ORs，并将该方法与异源细胞中表达的ORs的功能表达相结合，以识别大量的气味-气味组合。该项目将通过识别不同气味的受体库来推进我们对周围气味编码的理解，其中一些气味会引发刻板行为。这项研究产生的资源将是嗅觉领域许多研究人员的基础，他们对气味编码、行为和前受体事件感兴趣。这一新策略旨在全面确定一系列的气味，将广泛适用于许多其他气味的研究和跨越不同的物种。

DESCRIPTION (provided by applicant): The mammalian olfactory system has evolved to detect and discriminate amongst a myriad of volatile odor molecules as well as to respond to chemical cues from food, toxins, mates or predators to maximize fitness by utilizing a large family of odorant receptor (OR) proteins, members of G protein- coupled receptors. The mapping between ORs and corresponding odorants is, however, very complex: a given OR can be activated by more than one odor, just as one odor can activate an ensemble of ORs. The large number of receptors and odors, together with the multiple-to-multiple mapping relationships, make the systematic identification of odor-OR pairs a daunting task. Despite the success our lab and others have had in mapping odors to receptors by heterologous cell expression techniques, few studies have validated these in vivo. Here, we propose to develop a method to map ORs activated by odor stimulation in awake behaving animals, and use the method in combination with functional expression of ORs expressed in heterologous cells to identify a large set of odor-odorant combinations. This project will advance our understanding of peripheral odor coding by identifying the receptor repertoires of diverse odors, some of which elicit stereotypical behaviors. The resources generated by this study will be fundamental to many researchers in the olfaction field, who are interested in odor coding, behavior, and pre-receptor events. This new strategy aimed at comprehensively identifying a repertoire of ORs will be broadly applicable to the study of many other odorants and across diverse species.