The mammalian olfactory system is able to detect and discriminate a remarkable array of odorous molecules (odorants). Even slight changes in odorant structure can result in dramatically different perceived odors. Odorants are detected in the olfactory epithelium (OE) of the nose by olfactory sensory neurons (OSNs), which transmit signals to glomeruli within the olfactory bulb (OB) of the brain. From these, olfactory information is relayed to the primary olfactory cortex (OC) and to higher cortical areas. The initial events in odorant detect are mediated by the odorant receptors (ORs_, the largest known family of seven transmembrane domain (7TM), G protein-coupled receptors. Much has been learned about how OR input is organized in the OE and in the OB, but less is known about how olfactory information is extracted from the molecular structures of odorants. Moreover, nothing is known about how input from specific ORs is organized in the OC. I will use calcium imaging and single-cell PCR to identify ORs that distinguish closely related odorants belonging to different chemical and perceptual classes. In situ hybridization studies will determine how input from these ORs is routed in the OE and OB. Then, I will employ transgenic tracing techniques that utilize selected OR genes is routed in the OE and OB. Then, I will employ hybridization studies will determine how input from these ORs is routed in the OE and OB. Then, I will employ transgenic tracing techniques that utilize selected OR genes to explore how information about odorant structure is represented in the OC. These experiments should provide insight into the mechanisms that generate and process olfactory information and, ultimately, give rise to the conscious perception of odor.
