Transplantation of ventral forebrain cholinergic neurons to the hippocampus ameliorates impairment of radial-arm maze learning in rats with AF64A treatment.

Two types of cholinergic neurons were transplanted into the hippoccampus of adult rats chemically damaged by lateral ventricular administration of AF64A, a cholinergic neurotoxin, and the effects were compared with respect to their ability to reinnervate the hippocampus and to repair behavioral deficit. Pieces of brain tissue containing the nucleus basalis magnocellularis (NBM) or the striatum were taken for grafting from 17-day rat fetuses. About 3 months after transplantation, the rats with bilateral NBM grafts showed significant amelioration in radial-arm maze performance and habituation to a novel environment in an open field box, although they had not recovered to the control level. In rats with NBM grafts that showed a good performance, there were surviving grafts and many ingrowths of AChE-positive fibers in the hippocampus. By contrast, rats with striatal grafts showed hardly any significant improvement in these behavioral measures. The AChE staining revealed poor outgrowth of the striatal grafts into the hippocampus. These results indicate that grafting of NBM cholinergic neurons, which are anatomically similar to septal neurons, into the hippocampus produces a partial restorative effect on the cognitive impairment associated with hypofunction of the septohippocampal system.