Transient impairment of recognition memory following ibotenic-acid lesions of the basal forebrain in macaques

Abstract

To assess the contributions of the basal forebrain cholinergic nuclei to visual recognition memory in macaques, we compared the effects of lesions of (a) the nucleus basalis of Meynert, (b) the medial septal and diagonal band nuclei, and (c) all nuclei combined on performance of delayed nonmatching-to-sample with trial-unique stimuli. Whereas monkeys with the separate lesions did not differ from each other or from normal control animals, those with combined lesions showed a significant impairment. With time and extended practice, however, the performance of the animals with combined lesions recovered to normal levels. During the recovery period, these monkeys showed an initially increased sensitivity to scopolamine that later dissipated, at which time they also failed to show the improvement that follows physostigmine administration in normal animals. Postmortem assessment of cortical choline acetyltransferase activity revealed that only the group with combined lesions had significant depletion of this enzyme. The results suggest that (1) the basal forebrain cholinergic system participates in mnemonic processes in primates and that (2) extensive damage to this system is necessary before impairments in recognition memory, even transient ones, can be observed.