Temporal and Spatial Disparity in cFOS Expression and Dopamine Phenotypic Differentiation in the Neonatal Mouse Olfactory Bulb

Abstract

The mammalian olfactory bulb (OB) is among the few regions in adult brain which generates interneurons. A subpopulation of these phenotypically diverse interneurons is dopaminergic (DA) periglomerular cells. Full phenotypic development as indicated by expression of tyrosine hydroxylase (TH), the first enzyme in DA biosynthesis, requires afferent activity or equivalent depolarizing conditions. To investigate the hypothesis that cFOS regulates TH expression, this study analyzed OB slice cultures obtained from neonatal transgenic mice expressing 9 kb of TH promoter directing expression of green fluorescent protein (TH/GFP). Cultures were depolarized with 50 mM potassium chloride (KCl), the calcium channel blocker, nifedipine (10 microM) with KCl, or an equimolar concentration of sodium chloride (NaCl). Depolarization increased cFOS expression 6-fold peaking at about 3 h. Staining decreased rapidly returning to control, NaCl, levels by 48 h post-stimulation when TH/GFP expression was highest. Nifedipine blocked the increase in TH and cFOS suggesting that similar signal transduction pathways mediate both responses.