Specificity of fiber innervation by cholinergic neurons transplanted into the retrosplenial cortex of adult rats as revealed by choline acetyltransferase immunocytochemistry

The retrosplenial cortex (RSC) is a target of the forebrain cholinergic projecting system. It receives extensive cholinergic innervation from the medial septal nucleus and the diagonal band of Broca. These cholinergic afferents travel along the paths of cingulate bundle and fornix. In the present study we investigated the ability of cholinergic fetal septal grafts to reinnervate the deafferented RSC. Four groups of rats were used: (1) normal control rats (NC); (2) rats with bilateral transections of the cingulate bundle (CgX); (3) rats with simultaneous lesions of both the cingulate bundle and the fornix (FX), and (4) rats with intra-retrosplenial fetal septal grafts and lesions in both cingulate bundle and the fornix (RSCsep-TPL). We found that lesions in the cingulate bundle alone produced a modest reduction of cholinergic innervation whereas lesions in both the fornix and cingulate bundle resulted in a complete loss of cholinergic inputs in this area, indicating that both the cingulate bundle and the fornix are involved in mediating cholinergic projections from the septal-diagonal area to the RSC. Transplantation of cholinergic fetal septal neurons into the RSC of animals with simultaneous lesions in both the fornix and cingulate bundle restored the cholinergic innervation pattern to that which is typical of the normal septo-retrosplenial inputs. These results provide the neuroanatomical basis for behavioral studies which have documented graft-mediated recovery of spatial memory function in rats with lesions of the cholinergic septo-retrosplenial pathways.