EFFECTS OF EXCITOTOXIC LESIONS OF THE SEPTUM AND VERTICAL LIMB NUCLEUS OF THE DIAGONAL BAND OF BROCA ON CONDITIONAL VISUAL-DISCRIMINATION -RELATIONSHIP BETWEEN PERFORMANCE AND CHOLINE-ACETYLTRANSFERASE ACTIVITY IN THE CINGULATE CORTEX

Four experiments examined the role of the cholinergic projections from the septum and vertical limb nucleus of the diagonal band of Broca (V DB)in acquisition and performance of a conditional visual discriminati on. In experiments 1-3, excitotoxic lesions were made of the septum an d VDB in rats using quisqualic acid, which resulted in significant red uctions in ChAT activity in the hippocampus and cingulate cortex, but with no effects on cortical monoamines. In experiment 1, there were si gnificant impairments in acquisition of the conditional discrimination , which did not result from motivational impairments. Experiment 2 rep eated these results with lesion parameters, which produced variable ef fects on hippocampal and cingulate ChAT activity. Those rats with redu ctions in predominantly cingulate ChAT were most impaired in acquisiti on, but those with predominantly hippocampal reductions were relativel y unimpaired. Experiment 3 showed that quisquate-induced lesions of th e VDB, but not of the more caudal VDB and horizontal limb nucleus of t he diagonal band, produced deficits, and a model incorporating the res ults of experiments 1-3 showed a highly significant correlation betwee n errors of commission and cingulate cortical ChAT activity (r = -0.82 , p < 0.001). Experiment 4 used the excitotoxin AMPA to lesion the VDB in rats pretrained on a modified form of the conditional discriminati on task. In one subgroup of rats this excitotoxin produced profound an d regionally selective reductions in ChAT activity. This subgroup was also impaired in relearning the discrimination to criterion. Again, th ere was a significant inverse relationship between the number of error s of commission made in relearning the discrimination and cingulate Ch AT activity (r = -0.94, p < 0.001). These experiments suggest that exc itotoxic lesions of the septum/VDB produce deficits in conditional dis crimination learning and performance, and that the integrity of the pr ojection to the cingulate cortex is more crucial than that to the hipp ocampus in this effect. Moreover, there is a close relationship betwee n discrimination performance and cholinergic function in the cingulate cortex. In conjunction with other results, these data suggest that di fferent aspects of cognition and memory are modulated by cholinergic a ctivity in different cortical regions.