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.
This project will provide a comprehensive understanding of how G protein-coupled odorant receptors recognize and discriminate among odor ligands. This basic knowledge will advance the present understanding of G protein-coupled receptors, which are the largest molecular class of pharmaceutical targets for cardiac, psychiatric, and cancer diseases.
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