ER81 and CaMKIV identify anatomically and phenotypically defined subsets of mouse olfactory bulb interneurons

Department of Molecular Genetics, Institute of Biomedical Sciences, Fukushima MedicalUniversity, Fukushima, Japan 960-1295ABSTRACTThe mechanisms underlying dopamine (DA) phenotypic differentiation in the olfactory bulb(OB) have not yet been fully elucidated and are the subject of some controversy. OB DAinterneurons destined for the glomerular layer were shown to originate in the subventricularzone (SVZ) and in the rostral migratory stream (RMS). The current study investigated whethercalcium/calmodulin-dependent protein kinase IV (CaMKIV) either alone or together with the Etstranscription factor ER81 was necessary for phenotypic determination during migration ofprogenitors. In most brain areas, including the OB, CaMKIV and ER81 displayed a reciprocaldistribution. In the SVZ, only ER81 could be demonstrated. In the RMS, a subpopulation ofprogenitors contained ER81, but few, if any, contained CaMKIV. In OB, CaMKIV expression,restricted to deep granule cells, showed limited overlap with ER81. ER81 expression was weakin deep granule cells. Strong labeling occurred in the mitral and glomerular layers, where ER81colabeled dopaminergic periglomerular cells that expressed either tyrosine hydroxylase (TH) orgreen fluorescent protein, the latter reporter gene under control of 9-kb of 5 TH promoter. Odordeprivation resulted in a significant 5.2-fold decline in TH immunoreactivity, but ER81 exhibiteda relatively small 1.7-fold decline in immunoreactivity. TH expression as well as brain and bulbsize were unchanged in CaMKIV knockout mice. These data suggest that ER81 may be requiredbutisnotsufficientforDAneurondifferentiationandthatCaMKIVisnotdirectlyinvolvedinTHgene regulation. J. Comp. Neurol. 502:485–496, 2007.