In situ hybridization studies in the applicant's laboratory show that regional changes in the expression of mRNAs for the immediate early genes (IEGs) c-fos and c-jun provide a unique map of cell activation in the odor- stimulated olfactory bulb. Although the distribution of regions of increased IEG mRNA content differ between odors, the common translaminar pattern of activation suggests the presence of a basic functional/anatomical unit of odor representation in olfactory bulb. The goals of the proposed research are to further characterize this functional unit and to exploit this mapping technique to examine the maturation and influence of experience on this level of odor representation. Seven studies are proposed. (1) The spatial distribution and cellular localization of odor-elicited increases in mRNAs for c-fos, c-jun, and NGFI-A in main olfactory bulb will be evaluated to determine if there is a stereotypic columnar pattern of cell activation and whether odor intensity influences the parameters of this response. (2) The influence of learning on the pattern of c-fos mRNA induced by acute odor exposure will be evaluated to determine if odor preference learning alters the representation of the sensory cue. (3 & 4) The influence of simultaneous presentation of 2 novel olfactory cues (exp. 3) and the simultaneous presentation of one learned and one novel cue (exp. 4) will be examined to determine if the functional response to a mixed odor reflects competitive interactions (via lateral inhibitory circuits), and if the responses to familiar odors dominate when presented in conjunction with unfamiliar odors. (5) The influence of odors on IEG induction in immature rats will be examined to determine if the functional representation of specific odors becomes more sharply defined with age. In addition, the effects of olfactory deprivation during development will be examined to determine if sensory experience plays a role in the development of functional topography. (5 & 6) Finally, to begin to assess possible long-term effects of odor-induced changes in IEG expression, exps. 5 and 6 will determine if odors increase c-fos mRNA in enkephalin- and tyrosine hydroxylase- synthesizing neurons (exp. 5) and if odor-induced increases in c-fos expression are linked to changes in expression of mRNAs encoding preproenkephalin and tyrosine hydroxylase (exp. 6). Throughout, in situ hybridization of 35S-cRNA probes will be used to evaluate levels, regional distribution, and cellular localization of the mRNAs under analysis. The proposed studies should add to our understanding of the functional organization of olfactory bulb and how the functional map of odor representation matures under the influence of sensory experience. Moreover, the studies examining the link between c-fos and putative target gene expression could provide insight into cellular mechanisms whereby rapidly transient changes in IEG expression could effect more enduring changes in the functional properties of olfactory circuitry.
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