Grafted septal neurons form cholinergic synaptic connections in the dentate gyrus of behaviorally impaired aged rats

A group of aged, behaviorally impaired rats received suspension grafts of fetal septal-diagonal band tissue into the otherwise intact hippocampal formation. Three months after grafting, behaviorally recovered rats were studied by immunocytochemistry by using monoclonal antibodies to choline acetyltransferase (ChAT) and electron microscopy. The innervation of the host dentate gyrus by graft-derived ChAT-positive fibres was unmasked by acute removal of the intrinsic septal cholinergic innervation by fimbria-fornix transection 5-7 days before perfusion. The pattern of termination and ultrastructural connectivity were compared with previous results obtained from both young nonoperated control animals and a group of young rats with intrahippocampal septal grafts that had been subjected to denervation of the intrinsic cholinergic input at the time of transplantation. Graft-derived, ChAT-immunoreactive terminals formed abundant synaptic specializations with neuronal elements in the host dentate gyrus. The predominant postsynaptic target (about 65% of all boutons) was dendritic shafts, whereas about 20% of the boutons contacted dendritic spines. Very few synapses onto neuronal perikarya were found in the grafted aged rats. In some of these cases, however, it was possible to identify the target as dentate granule cells. This situation is very similar to that seen in young control rats but significantly different than the distribution observed in the denervated young grafted group, where axosomatic contacts predominated. The results indicate that the graft-induced behavioral improvement seen in the aged rats may depend on the formation of functional cholinergic graft connections with neuronal elements in the host hippocampal formation.