BEHAVIORAL-EFFECTS OF BASAL FOREBRAIN GRAFTS AFTER DORSAL SEPTOHIPPOCAMPAL PATHWAY LESIONS

There are many reports that basal forebrain grafts ameliorate behavior al impairments produced by dorsal septo-hippocampal pathway lesions, b ut several studies have either found that this recovery may be unrelat ed to concomitant restitution of cholinergic markers, may be modest an d depend on certain experimental conditions, or instead that grafts ma y actually exacerbate lesion-induced impairments. In this study, rats received one of three lesions of the dorsal septo-hippocampal pathways or a sham lesion, at 32 days of age, and intrahippocampal basal foreb rain grafts or the vehicle control 10 days later. In grafted rats with total aspirative lesion of the fimbria-fornix, there was a substantia l AChE-positive hippocampal reinnerivation but no improvement of the s evere lesion-induced spatial learning deficits, either reference memor y or working memory, whether tested at 1 or 5 months post-grafting. In rats with bilateral medial fimbria lesions, grafts were successful, n ormal in appearance and produced substantial hippocampal cholinergic r einnervation; relative to non-grafted counterparts, however, grafted m edial fimbria rats showed an early reference memory impairment and a p ersistent exacerbation of a working memory deficit. Exacerbation of le arning impairments was also apparent in grafted rats with partial hipp ocampal denervation due to lesion of the cingulate and adjacent cortex above the fimbria-fornix. Nonetheless, basaI forebrain grafts normali sed general activity in these lesion groups, irrespective of whether t he lesion-induced change was an increase or a decrease relative to con trols. Graft-derived AChE-positive innervation was more marked than ex pected in both grafted cingulate-lesioned rats and grafted sham-lesion ed rats, while control grafts of fetal cortex (above the septum) produ ced little or no AChE-positive innervation. Size of basal forebrain gr afts, originally 3 mu l at two dorsal sites per hippocampus, increased markedly from rostral to caudal dorsal hippocampus in all groups but did not differ significantly across grafted groups, even with respect to non-lesioned rats. This study adds further evidence that basal fore brain grafts, successful with respect to cholinergic reinnervation, do not always enhance cognitive functions in rat hippocampal lesion mode ls, and confirms that these grafts may have adverse effects after part ial septo-hippocampal system lesions. It is important to attend to bot h the potential negative and positive effects of neural grafts.