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.