Unique regulation of immediate early gene and tyrosine hydroxylase expression in the odor-deprived mouse olfactory bulb

Tyrosine hydroxylase (TH), expressed in a population of periglomerular neur ons intrinsic to the olfactory bulb, displays dramatic down-regulation in r esponse to odor deprivation. To begin to elucidate the importance of immedi ate early genes (IEG) in TH gene regulation, the present study examined exp ression of IEGs in the olfactory bulb in response to odor deprivation. In a ddition, the composition of TH AP-1 and CRE binding complexes was investiga ted in control and odor-deprived mice. Immunocytochemical studies showed th at c-Fos, Fos-B, Jun-D, CRE-binding protein (CREB), and phosphorylated CREB (pCREB) are colocalized with TH in the dopaminergic periglomerular neurons . Unilateral naris closure resulted in down-regulation of c-Fos and Fos-B, but not Jun-D, CREB, or pCREB, in the glomerular layer of the ipsilateral o lfactory bulb. Gel shift assays demonstrated a significant decrease (32%) i n TH AP-I, but not CRE, binding activity in the odor-deprived bulb. Fos-B w as found to be the exclusive member of the Fos family present in the TH BP- l complex. CREB, CRE modulator protein (CREM), Fos-B, and Jun-D, but not c- Fos, all contributed to the CRE: DNA-protein complex. These results indicat ed that Fos-B, acting through both AP-1 and CRE motifs, may be implicated i n the regulation of TH expression in the olfactory bulb dopaminergic neuron s.