RESTORATION OF COGNITIVE-ABILITIES BY CHOLINERGIC GRAFTS IN CORTEX OFMONKEYS WITH LESIONS OF THE BASAL NUCLEUS OF MEYNERT

Three groups of marmosets were trained to perform a series of visual d iscrimination tasks in a Wisconsin General Test Apparatus, Two groups then received bilateral lesions of the basal nucleus of Meynert using the excitotoxin N-methyl-D-aspartate and were found to be severely imp aired on relearning a visual discrimination first learnt prior to surg ery. One lesioned group then received grafts of acetylcholine-rich tis sue dissected from the basal forebrain of fetal marmosets. Three month s later the marmosets with lesion alone remained impaired on a number of retention and reversal tasks whereas the transplanted animals were no longer significantly impaired. Histological examination of the brai ns indicated that all lesioned animals had sustained substantial loss of the cholinergic neurons of the basal nucleus of Meynert (assessed b y nerve growth factor receptor immunoreactivity) and that the lesion-a lone animals showed marked loss of the cholinergic marker acetylcholin esterase in the dorsolateral frontal and parietal cortex. All transpla nted animals had surviving graft tissue (visualized by Cresyl Violet s taining, dense acetylcholinesterase staining and the presence of a lim ited number of nerve growth factor receptor-immunoreactive neurons) in the neocortex and 5/6 transplanted animals showed near complete resti tution of acetylcholinesterase staining in frontal and parietal cortex . Examination of individual animal data showed that the animal without this restitution performed very poorly. The performance of the remain ing transplanted animals was significantly better than that of the ani mals with lesion alone. There was a significant positive correlation b etween the degree of acetylcholinesterase staining and good performanc e on tasks sensitive to frontal lobe damage.These results demonstrate that acetylcholine-rich tissue transplanted into the neocortex of prim ates with damage to the cholinergic projections to the neocortex can p roduce substantial restitution of function provided that an appropriat e level of interaction between graft and host tissue is achieved.