Recent in situ hybridization studies in the applicant's laboratory show that regionally discrete 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. Moreover, although different odors stimulate regionally distinct increases in IEG mRNA content, the common vertical pattern of activation within a region (i.e., narrow in the glomerular layer and successively wider in the granule and mitral cell layers) suggests that presence of a basic functional/anatomical unit of odor representation in the olfactory bulb. The major goals of the proposed research are to test this possibility, to examine factors which may influence the spatial distributions of activation in the different bulb laminae, and to explore the possibility that in association with increased expression of transcriptional regulatory products encoded by IEGs, odors stimulate regional increases in the expression of transcriptional regulatory products encoded by IEGs, odors stimulate regional increased expression of transcriptional regulatory products encoded by IEGs, odors stimulate regional increases in the expression of neurotrophic factors. Five 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 vertical (columnar) pattern of activation that is independent of the particular odor used or region of bulb evaluated. (2) The influence of different durations and patterns of odor presentation on IEG expression will be evaluated to determine i) the threshold to induction, ii) the influence of stimulus duration on the spatial distribution of activation and iii) whether the IEG response of bulb neurons becomes refractory to repeated odor stimulation. (3) The influence of centrifugal afferents in shaping the fields of odor-elicited increases in IEG mRNA expression in the bulb will be evaluated in studies employing electrolytic and ibotenic acid lesions of afferent groups. (4) The influence of the NMDA receptor antagonist AP5 will be evaluated to test the hypothesis that this receptor type is involved in the odor stimulation of IEG expression by some, but not all, bulb cell types. (5) Finally, to test the hypothesis that olfactory stimulation, and odor-elicited increases in IEG expression, regulate the expression of neurotrophic factors, the influence of olfactory deprivation and of specific odor presentation on levels of mRNAs for nerve growth, brain derived neurotrophic factor, and insulin-like growth factor-I in olfactory bulb neurons will be examined. Throughout, in situ hybridization of 35S-cRNA probes will be used to evaluate levels, regional distribution, and cellular localization of mRNAs under analysis. The proposed studies should add significantly to our understanding of the functional organization of the olfactory bulb and may elucidate general principles of sensory representation in the CNS. Moreover, the studies of neurotrophic factor expression could reveal processes underlying the anatomical plasticity that goes on in the bulb throughout life.
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