Odorant receptor organization and information coding in the mouse olfactory system

Olfaction is unique among the senses. Thousands of different odorant molecules are able to elicit uniquely different perceptual responses in the olfactory world of an organism. What are the neural mechanisms which allow the brain to encode and interpret the complexity of odorant information? A long standing view has been that a more complete understanding of the functional organization of neural space in the olfactory epithelium and olfactory bulb would lead to a greater understanding of olfactory information coding.; The existence of an extremely large family of odorant receptor genes suggests that olfactory discrimination must rely heavily on the differential binding properties of hundreds of different receptors. I have cloned mouse odorant receptor genes for use as molecular probes of spatial organization in the olfactory system. Using in situ hybridization with these odorant receptor probes, I have found that neurons expressing different receptors are segregated into at least four different spatial zones in the olfactory epithelium. Each olfactory sensory neuron may only be able to express a single type of odorant receptor. Within each zone, neurons expressing the same receptor appear to be randomly organized, so that each zone contains a mosaic of hundreds of different types of receptors. Comparison of our data with existing anatomical data suggests that this initial zonal organization of olfactory information is maintained in the projection to the olfactory bulb.; We have found that sensory axons within the olfactory bulb can, like neurons in the epithelium, be labeled by in situ hybridization with odorant receptor probes. This analysis has shown that hundreds to thousands of neurons expressing the same odorant receptor type that are broadly distributed in the epithelium project in a convergent fashion to only a few glomeruli within the olfactory bulb. Each glomerulus may only receive input from neurons of the same receptor type, and the relative locations of these glomeruli may be stereotyped in different animals. Thus, olfactory information provided by the odorant receptors is mapped in a precise and perhaps stereotyped way in the olfactory bulb.; During embryonic mouse development, we have shown that different types of odorant receptors are initially expressed at roughly the same time. This initial onset of receptor expression occurs before synaptogenesis between sensory axons and their targets in the presumptive olfactory bulb. Furthermore, normal receptor expression occurs in the absence of an olfactory bulb. These experiments suggest that temporal and target influences do not determine the specific odorant receptor expressed by the sensory neuron. Rather, receptor choice occurs before and is possibly causal to the choice of glomerular target in the bulb.; I have created odorant receptor producing retroviruses as a tool for studying the molecular mechanisms of axonal targeting. I have used retroviral gene transfer of odorant receptor genes to ask if specific odorant receptor expression is sufficient for axonal targeting to a specific glomerulus. Preliminary evidence is consistent with the hypothesis that odorant receptor gene expression influences axonal targeting within the olfactory bulb.; The use of odorant receptors as molecular probes has provided a successful tool in revealing previously unknown spatial patterning in the olfactory system. These patterns of receptor expression have provided new insights into how molecular information might be represented in the nose and in the olfactory bulb of the brain.