Postnatal development of the serotonin innervation of the hippocampus and dentate gyrus following raphe implants.

Serotoninergic (5-HT) neurons derived from the embryonic raphe nuclear area (brainstem, embryonic days (E 16-18) were implanted into the entorhinal cortex of 6-day-old (P6) neonatal rat recipients which had received a fimbria lesion and entorhinal cortex ablation on P3. The hippocampus, dentate gyrus, and the raphe implant area were examined with 5-HT immunohistochemistry 7, 14, 21, 30, and 60 days after implantation. The pattern of 5-HT reinnervation was compared to that of normal and lesioned animals, and to previous studies in which rats received septal or striatal implants. In the hippocampus adjacent to the implant 5-HT-immunoreactive fibers were first observed by 7 days postimplantation and increased in density and in their septotemporal and dorsoventral extent with increasing time postimplantation. Moderately dense fiber networks were diffusely distributed in the hippocampus and dentate gyrus at 30 and 60 days postimplant. Little, if any, indication of lamination was present. Retrogradely labeled neurons (the majority of which contained 5-HT immunoreactivity) were observed in the raphe implant following injections of Fast Blue into the hippocampal formation. A few retrogradely labeled cells did not contain 5-HT, methionine-enkephalin (ME), or substance P (SP) immunoreactivity, although ME- and SP- immunoreactive neurons were observed in the implants. The lamination patterns and the increased density of 5-HT-immunoreactive fibers following a raphe implant into the entorhinal cortex clearly differ from the normal 5-HT pattern and from the patterns of lamination following a striatal or septal implant.