Molecular Analysis of Olfactory Sensory Imputs

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DESCRIPTION (From the Applicant's Abstract): The olfactory system resembles other sensory systems in its ability to translate sensory stimuli into distinct perceptions. However, it offers unique opportunities to use molecular approaches to elucidate how information is extracted from sensory stimuli and then organized in the brain to yield different perceptions. This opportunity stems from the finding that odorant detection is mediated by approximately 1000 different odorant receptors (ORs), which are expressed by olfactory sensor neurons (OSNs) in the nasal olfactory epithelium (OE). From the OE, signals are relayed through the olfactory bull (OB) and then the olfactory cortex (OC) to other brain areas. Each OSN expresses one OR gene. In the OE, 4 zones express different sets of ORs. OSNs expressing the same OR are scattered in one zone. However, their axons converge in a few specific OB glomeruli, generating a precise map of OR inputs. The functional significance of the patterning of the OE and OB is not yet understood, nor is it known how OR inputs are organized beyond the OB. Another important question is how information about diverse odorant structures is organized to yield different odor perceptions. Recently we found that different odorants are recognized by different combinations of ORs. A single odorant was recognized by both highly related and divergent ORs, and some ORs distinguished among odorants that differed by a single functional group whereas others did not. In the studies described in this proposal, we will further explore how olfactory information is obtained from odorant structures by the OR family. We will also examine how that information is organized in the olfactory system. We will first use a combination of calcium imaging of OSNs and single cell PCR to identify ORs for n-aliphatic odorants that have the same carbon chains, but a variety of different functional groups. We will then express each of the ORs in a cell line and further characterize their odorant specificities. Based on our previous findings, we expect to identify both highly related and divergent ORs, some of which will distinguish odorants that differ in functional group and others that will not. Using in situ hybridization, we will then ask whether there are correlations between the function of an OR, or its structure, and either zones in the OE or the particular arrangement of glomeruli in the OB. Finally, we will use gene targeting to generate mice that coexpress a transneuronal tracer with a single OR gene in order to determine how inputs from individual ORs are organized in the OC and whether inputs from ORs for odorants with different functional groups are targeted to specific cortical regions.