Memory related role of the posterior cholinergic system

Abstract

In order to establish a model for the possible neuropathology of patients with Alzheimer's disease, various behaviors of rats with different chemical lesions in cholinergic regions were studied and compared with those of sham-operated control rats. A battery of neurological tests was used as well as activity measurements and two learning tasks: a positively reinforced place-learning task with delay periods of 0 s, 1 min, 15 min, and 2 h, and a shock-motivated two-way active avoidance task. While in general no intergroup differences were obtained in performance on the neurological test battery or the rats' activity in an open field, there were marked impairments in the three lesioned groups compared to the control group in the two learning tasks. These deficits were less severe in the two groups with lesions of the medial septal/vertical diagonal band of Broca region and the nucleus basalis of Meynert region, but rather marked in the group with lesions of neurons situated in the pontomesencephalic region, although the amount of ibotenic acid injected had been the same for all groups. We conclude from these data that changes in mesencephalic cholinergic regions might play a significant role in the pathology of Alzheimer's disease. The existence of such regions was recently established for primates as well, thus providing a basis for justifying an animal model of this human disease.