Richard Axel's laboratory is interested in the transformations that translate odor binding in the periphery into neural activity in olfactory centers in the brain. Olfactory perception is initiated by the recognition of odors by a large repertoire of receptors in neurons of the sensory epithelium. The representation of neural activity in the nose is converted into an insular, segregated map in the olfactory bulb that exhibits chemotopic relationships. This transformation results from the convergence of like axons, each bearing the same receptor, on a given glomerulus. This organization combines the robustness of a redundant, spatially unbiased sampling system in the nose with the economy of a condensed spatial representation in the olfactory bulb. Optical imaging of responses in the cortex reveals a second transformation in which odors activate a sparse subpopulation of neurons distributed across the piriform cortex. The piriform therefore discards chemotopic, spatial segregation and returns to a highly dispersed organization in which different odors activate a unique ensemble of cortical neurons.
Representations of the Olfactory World in the Brain
Individual olfactory sensory neurons express only 1 of about 1,000 odorant receptor genes. The choice of a specific odorant receptor defines the functional identity of a sensory neuron, and the receptor also provides an instructive cue that dictates the site of projection in the brain. Thus the expression of a single receptor gene in a sensory neuron is an essential feature of olfactory perception. Recently, we have demonstrated that a regulatory element on chromosome 14 in the mouse associates with multiple odorant receptor promoters on different chromosomes. These data suggest a model of receptor gene choice in which a single transacting regulatory element may allow the stochastic activation of only one receptor allele in an olfactory sensory neuron. We wish to discern the mechanism of this novel pathway of regulation in trans rather than cis. What proteins facilitate the trans-association of a singular regulatory element with multiple odorant receptor promoters? Finally, we wish to determine whether this mechanism is more generally employed to choose one gene from other large gene families.