ADULT NARIS CLOSURE PROFOUNDLY REDUCES TYROSINE-HYDROXYLASE EXPRESSION IN MOUSE OLFACTORY-BULB

Peripheral afferent innervation appears to be required for the expression of the dopamine phenotype in the rodent main olfactory bulb. Experiments utilizing neonatal naris closure as a means of sensory deprivation also suggest that odor-induced afferent activity is required for the expression of the phenotype. These experiments are confounded, however, by the significant postnatal maturation of the dopamine system. The current experiments utilized adult unilateral naris closure to address this issue. As with neonatal closure, adult deprivation produces a profound reduction in the expression of tyrosine hydroxylase (TH), the first enzyme in the dopamine biosynthetic pathway. By 4 days a small decrease is observed in TH activity and immunoreactivity. Activity reaches a nadir of 12% of control levels at about 1 month. TH mRNA is reduced similarly when analyzed at about 2 months post-closure. Glutamic acid decarboxylase protein and mRNA expression, which are co-localized with TH, remain at close to control levels indicating the continued presence of the dopamine neurons. The time-course of the loss of TH is identical to that for zinc sulphate-induced denervation of the olfactory bulb. These data support the hypothesis that odor modulated afferent activity is required for expression of the dopamine phenotype and that, if a trophic factor is involved, its release is also activity dependent.