Severe learning impairment caused by combined immunotoxic lesion of the cholinergic projections to the cortex and hippocampus in monkeys

Monkeys with immunotoxic lesions of both the basal nucleus of Meynert and t he vertical limb of the diagonal band of Broca (NBM + VDB) lost cholinergic innervation throughout the cortex rind hippocampus. They were impaired at learning discriminations between objects differing in either few, or many, attributes and at learning visuospatial conditional discriminations. Monkey s with immunotoxic lesions of the NBM lost cholinergic innervation of the n eocortex only. Initially, they were unable to learn a simple visual discrim ination where the stimuli differed in a limited number of attributes but th ey were unimpaired at learning discriminations between objects that differe d in more attributes. They were mildly impaired at learning a visuospatial conditional task. The impairment exhibited by monkeys with lesions of the N BM alone ameliorated with time but that following NBM + VDB lesions did not . previous experiments have shown that monkeys with immunotoxic lesions of the VDB alone are impaired at learning visuospatial conditional discriminat ions but an unimpaired at learning simple visual discriminations. When monk eys with NBM lesions were given excitotoxic lesions of the CA1 field of the hippocampus the learning impairment on discriminations between objects whi ch differed in few attributes was reinstated. Pretreatment with a cholinerg ic agonist improved learning ability on visual discrimination learning in a ll monkeys but this improvement was significantly greater in monkeys with l esions of the NBM. On conditional discrimination learning, which is particu larly sensitive to hippocampal damage, pilocarpine produced a significant i mprovement in monkeys with NBM + VDB lesions (where the hippocampal dysfunc tion was cholinergic) but not in monkeys with NBM + CA1 lesions (where the hippocampal damage was structural). (C) 1999 Elsevier Science B.V. All righ ts reserved.