Studies on the role of the serotonergic neuron system in the plasticity of the developing brain

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Serotonin (5-HT) is related to the plasticity of the brain, and 5-HT heterotypic sprouting occurs in the neostriatum of rats that suffer 6-hydroxydopamine (6-OHDA) lesioning in the neonatal period. 6-OHDA was administered to the right lateral ventricle of animals (rat and mouse) at 3 days, 7 days, 12 days and 28 days after birth. Then the animals were perfused transcardially at 2 days, 5 weeks, 10 weeks and 1 year after the administration of 6-OHDA.Immunohistochemical studies were performed with anti-tyrosine hydroxylase (TH) and anti-5-HT antibodies. NADPH-diaphorase histochemistry was also performed. Quantitative analysis on NADPH-positive cells and fiber terminals were performed using NIH Image at three coronal levels.This study has shown that remarkable hyperinnervation of serotonin fibers occurred in the striatum of mice that had undergene the same kind of unilateral 6-OHDA lesioning at even 12 days after birth. This is an important finding as to the critical period for serotonergic heterotypic sprouting after dopamine denervation. Noteworthy is that intrinsic serotonergic heterotypic sprouting persisted throughout the time course of the study, namely, to one year after 6-OHDA lesioning, suggesting that the sprouting is long lasting. There is no significant change in the density of NADPH-positive structures in the striatum during the development of serotonergic heterotypic sprouting after dopamine-depletion. This is the first demonstration that 5-HT hyperinnervation occurs in the neostriatum of mice suffering 6-OHDA lesioning at even 12 days after birth, and that 5-HT heterotypic sprouting may be permanent.