Multiple lines of evidence support the notion that the axons from olfactory receptor neurons expressing the same odor receptor (OR) largely converge onto only 2 or a few glomeruli in the olfactory bulb. To accomplish this there is an extraordinary reorganization of axons that occurs between the olfactory epithelium and the olfactory bulb. The pathfinding exhibited by axons during reorganization as well as their targeting of specific glomeruli appears to be influenced, at least in part, by the unique OR expressed by any single olfactory receptor neuron. Thus, ORS constitute a unique set of molecular tags/determinants that provide an exciting opportunity to study further the organization of the glomerulus and its role in odor processing. . Moreover, because of recent advances in protein tracking technology, the opportunity is presented to investigate the spatio-temporal proteins of ORS in olfactory receptor neurons in order to understand if their intracellular distribution is consistent with a determinant role in axon guidance.
Three specific aims are proposed: 1) Does one specific gene, coding an OR sequence, uniquely define all of the afferent axons projecting to one glomerulus? Using Lac-Z constructs, the synaptic organization of axons expressing specific ORS will be studied. 2) What is the distribution of mitral cells whose apical dendrites innervate a specific glomerulus? While some evidence suggests that the somata of these mitral cells should be contiguous, the hypothesis has not been addressed. Green Fluorescent Protein constructs can be employed to identify the afferent axons converging on specific glomeruli. Identified glomeruli will be infected with fluorescent or light-dense tracers to map the distribution of mitral cells whose dendrites are innervating the identified glomerulus. 3) What is the intracellular distribution of OR protein? While the evidence favoring multiple roles for ORS is compelling, it is not evident in which intracellular compartments OR protein is found. Using Green Fluorescent Protein coding sequence fusions with OR coding sequences, the spatio- temporal characteristics of OR protein products will be assessed to address this significant gap in our knowledge. Collectively, these studies will shed new light on the organization of primary olfactory projections, the role of the glomerulus in odor processing, the topography of higher order projections emerging from glomeruli and finally, the mechanisms that may govern the intracellular distribution of OR proteins. These results may be significant for people suffering from anosmia and hyposmia, Kalman's Syndrome and related diseases of axon guidance.
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