NEURAL GRAFTING OF CHOLINERGIC NEURONS IN THE HIPPOCAMPAL-FORMATION

The cholinergic septohippocampal system plays an important role in spa tial learning and memory functions. Transections of the septohippocamp al pathway have been shown to result in a near complete loss of cholin ergic innervation in the hippocampus and induce severe spatial memory impairments. In this article, we have reviewed the studies which demon strate the ability of intrahippocampal septal grafts to reinnervate th e hippocampal formation and ameliorate spatial learning and memory def icits. Neuroanatomical studies suggest that grafts of cholinergic tiss ue can innervate the host hippocampal formation in a pattern that mimi cs that of the normal septohippocampal pathway. This innervation, in t urn, is associated with the formation of graft-to-host synaptic connec tions. Neurochemical studies reveal that intrahippocampal grafts of se ptal cells can restore choline acetyltransferase activity, acetylcholi ne synthesis, and high affinity choline uptake in presynaptic terminal s of grafted neurons. In addition, these grafts can normalize the upre gulation of cholinergic muscarinic receptors seen postsynaptically in the hippocampus following lesions of the septohippocampal pathway. The functional nature of these grafts is also substantiated by electrophy siological recordings which demonstrate stimulus-evoked graft-to-host synaptic transmission as well as the reinstatement of EEG activity typ ical of septohippocampal connectivity. In addition to graft-to-host co nnections, behavioral and neurochemical studies also provide evidence for host-to-graft connections that can regulate the activity of grafte d cholinergic neurons during the performance of specific behavioral ta sks requiring spatial memory function. Together, these studies suggest that grafts of cholinergic neurons from the medial septal nucleus can become anatomically and functionally incorporated into the circuitry of the host hippocampal formation.