CHOLINERGIC RE-INNERVATION OF THE RAT HIPPOCAMPUS BY SEPTAL IMPLANTS IS STIMULATED BY PERFORANT PATH LESION

Transplants taken from the septal-diagonal band area of rat embryos have previously been shown to innervate the cholinergically denervated hippocampus when implanted into a cavity made through the hippocampal fimbria in adult recipient rats. In animals where the perforant path afferents to the hippocampus are left intact, the growth of cholinergic axons from the implant into the hippocampus levels off after one month and the axons stop growing before the entire denervated target has been reinnervated. In the present study we report that an additional lesion of the perforant path stimulates the ingrowth of cholinergic axons into the cholinergically denervated hippocampus, causing the axons of the cholinergic neurons in the implant to grow both at a faster rate and for a prolonged period of time. The marked increase in the recovery of the acetylcholine synthesizing enzyme, choline acetyltransferase, and in acetylcholine esterase staining, as observed 2 and 4 months after transplantation, indicates that the end result in an increase in the total number of cholinergic fibres formed in the hippocampus of the perforant path lesioned rats. The histochemistry, moreover, reveals that the stimulated axon ingrowth is mainly confined to the part of the dentate gyrus denervated of its perforant path input, i.e. the outer 60% of the dentate molecular layer. These observations point to basic similarities between the factors triggering collateral or paraterminal sprouting from intact nature axons and the mechanisms governing the formation of terminals patterns by ingrowing embryonic axons in the adult mammalian CNS. © 1979.