Formation of cholinergic synapses by intrahippocampal septal grafts as revealed by choline acetyltransferase immunocytochemistry

The ultrastructural features of the contacts established by intrahippocampal grafts of foetal septal/diagonal band neurones in the dentate gyrus and the CA1 region of the previously denervated host hippocampus have been analysed with electron microscopic immunocytochemistry using a monoclonal antibody to choline acetyltransferase (ChAT). The results show that the grafted ChAT-positive neurones are capable of forming extensive synaptic contacts with neuronal targets in areas of the dentate gyrus and CA1 which normally receive such innervation. While all types of contacts normally found in association with the granule and pyramidal cell layers were also present in the graft-reinnervated specimens, the quantitative relationship between somatic and dendritic synapses was abnormal. Thus, the ChAT-immunoreactive synapses on cell bodies, which amounted to only a few percent in the normal animal, constituted over 60% in the grafted animals. Conversely, synapses on dendrites which constituted over 90% in the normal dentate were reduced to less than 40% in the grafted animals. The postsynaptic targets of the graft-derived cholinergic synapses included dendrites and cell bodies of dentate granule cells and CA1 pyramidal cells. This supports previous electrophysiological studies and indicates that the septal grafts may be able to modulate host hippocampal function via direct efferent connections onto the granule and pyramidal neurons in the host hippocampal formation.