Innervation of embryonic hippocampal implants by regenerating axons of cholinergic septal neurons in the adult rat

The regeneration of the septal cholinergic system in adult rats has been studied in animals bearing transplants of hippocampus taken from 20–40 mm rat fetuses (approximately 17–21 days of gestation). The septal axons located within the fimbria and the dorsal fornix were lesioned and a cavity was prepared at the rostral end of the hippocampus. The embryonic tissue was placed adjacent to the severed end of the fornix-fimbria. The time-course of ingrowth of cholinergic fibers into the transplant was monitored by acetylcholine esterase (AChE) histochemistry and the determination of the levels of choline acetyltransferase (ChAT). Both methods indicate that there is a progressive ingrowth into the transplant of cholinergic fibers up to 3 months after transplantation. The newly-formed AChE-positive fibers in the transplant remain beyond one year after transplantation and are thus presumably permanent. Both horseradish peroxidase (HRP) injections into the implant and radiofrequency lesions of the septal-diagonal band area indicate that the principal source of these fibers is the AChE-positive neurons of the medial septum and the nucleus of the diagonal band which normally form the septohippocampal cholinergic projection. The results suggest: (1) that implants of a normal embryonic target tissue can promote axonal regeneration in mature neurons of the mammalian central nervous system; (2) that some neurons in the adult mammalian CNS retain at least part of their embryonic capacity to generate axons and recognize specific postsynaptic targets in developing CNS tissue; and (3) that this host-implant interaction can result in the formation of quite specific innervation patterns in the implanted target tissue.