MOLECULAR BASIS OF OLFACTORY DISCRIMINATION

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The mammalian olfactory system is able to discriminate a vast number and variety of different odors. The initial events in odor perception occur in ciliated olfactory sensory neurons that reside in a specialized olfactory epithelium in the nasal cavity. Odorous molecules (odorants) bind to odorant receptors on the cilia of these neurons and induce a cascade of events that leads to the transmission of signals to the olfactory bulb. It is thought that different subsets of olfactory neurons recognize different odorants and that the pattern of synapses formed by each subset in the olfactory bulb might be read as an 'odor code'. In fact, the organizational principles and molecular mechanisms that underlie the coding peripheral olfactory information are unknown. The missing key to understanding olfactory coding has been the odorant receptor. We have identified a multigene family in the rat that is likely to encode odorant receptors. We will now use this multigene family to perform studies that will provide insight into olfactory information coding. We will: 1) Analyze the functional properties of the putative odorant receptors by expressing individual receptors in heterologous cell types and studying the ability of the recipient cells to respond to different odorants. 2) Define the organizational principles underlying odor coding by determining how many different odorant receptor subtypes are expressed by individual olfactory neurons, characterizing the topographical patterns of expression of different odorant receptor subtypes in the olfactory epithelium, and analyzing the patterns of synapses formed in the olfactory bulb by neurons that express different receptor subtypes. 3) Investigate the developmental acquisition of these organizational features in order to determine the mechanisms by which they are established.