Organization of regenerating serotonergic fibers in the hippocampal formation

Abstract To evaluate the capacity of fiber outgrowth of serotonergic and dopaminergic neurons from the dorsal raphe tissue, the following three experiments were performed; (1) fetal mesencephalic raphe tissue was transplanted into the ventricle near the denervated hippocampal formation of adult rats, (2) fetal mesencephalic raphe and neonatal hippocampal tissues were transplanted into the anterior eye chamber of adult rats, and (3) fetal mesencephalic raphe tissue was explanted together with the neonatal hippocampal tissue. The extent of the fiber outgrowth was examined immunohistochemically using serotonin and tyrosine hydroxylase (TH) antisera. Three months after transplantation into the host brain, serotonin-immunoreactive (ir) fibers from raphe graft were densely distributed throughout the graft and in the host hippocampal formation, and TH-ir fibers were restricted to an area near the somata of TH-ir neurons. In particular, hyperinnervation of serotonin-ir fibers was observed in the molecular layer of the dentate gyrus. Two months after intraocular transplantation, mesencephalic raphe tissue contained a large number of serotonin- and TH-ir neurons and fibers. The distribution pattern of outgrowing serotonin-ir fibers in the hippocampal tissue was similar to that observed following intraventricular transplantation. Two weeks after explantation, the raphe tissue contained numerous serotonin-ir neurons and their fibers. These fibers extended into the hippocampal tissue in the same manner as the intraventricular and intraocular transplants. These results indicate that the intrinsic factors of hippocampal tissue influence the organization of serotonergic fibers in the hippocampal formation.