Postmitotic, postmigrational expression of tyrosine hydroxylase in olfactory bulb dopaminergic neurons

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Abstract
The developmental expression of tyrosine hydroxylase (TOH) was studied in a large, specific population of dopaminergic (DA) neurons in the main olfactory bulb (MOB) of the rat. These DA neurons comprise an anatomically distinctive population that has been well characterized in the adult hamster (Davis and Macrides, 1983) and rat (Halasz et al., 1981; Baker et al., 1983, 1984). We addressed a basic question in developmental neurobiology: What factors regulate the expression of neuronal transmitter phenotype during development? Olfactory bulb DA neurons are born in the ventricular and subependymal zones and migrate through all intervening layers to the most superficial layer in the bulb (Altman, 1969; Bayer, 1983). The time of TOH expression in these neurons was determined using immunohistochemistry and light microscopic image-analysis techniques. The results indicate that TOH phenotype is not expressed when the cells are born in the subependymal zone nor during their migration to the periglomerular region but only after they reached their final destination, the glomerular layer. This suggests that epigenetic factors associated with the glomeruli initiate the expression of the key transmitter synthesizing enzyme in these neurons. Primary olfactory neurons in the nasal epithelium project exclusively to glomeruli of the MOB; removal of this input in adult rats (Kawano and Margolis, 1982; Baker et al., 1983, 1984), mice (Nadi et al., 1981; Baker et al., 1983), dogs (Nadi et al., 1981), and hamsters (Kream et al., 1984) appears to down-regulate the expression of the TOH in periglomerular cells. The present results suggested that the input from the primary olfactory nerve is also necessary for the initial expression of the TOH phenotype. In support of this notion, we found that lesions of the olfactory nerve during the first postnatal week caused a significant reduction in the number of TOH-positive juxtaglomerular neurons in the following weeks. Thus, the olfactory nerve appears to be necessary for both the initiation and maintenance of TOH expression in olfactory bulb neurons. These findings suggest that specific cell-cell interactions play a key role in CNS neuronal transmitter phenotype regulation. The present study also demonstrated that there are significant postnatal changes in the number, size, and distribution patterns of MOB DA neurons. From birth to adulthood there is a linear increase of over 100-fold in the number of neurons expressing the TOH phenotype. There are about 1000 DA neurons per bulb at birth; in adulthood there are approximately 150,000 DA neurons per bulb. The average size of the TOH-immunoreactive cells decreases during development: from 12.1 .+-. 0.5 .mu.m in the neonate to approximately 10.0 .+-. 0.5 .mu.m in the adult MOB. This decrease in average size may be related to the fact that there are 2 populations of DA neurons in the adult MOB (Halasz et al., 1981; Baker, 1996; present report). Size histograms of developing and mature MOB DA neurons were generated, and the results suggest that the first MOB neurons to express the dopamine phenotype are probably external tufted cells, which are born earlier than the smaller, more numerous periglomerular neurons which express the phenotype later. The steady, prolonged increase in the number of neurons expressing the DA phenotype in MOB suggests that these neurons have a progressively important role during the development of olfactory function. This may be related to the steadily increasing ability of rats to discriminate different odors during the first postnatal month (Alberts, 1981).

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