BEHAVIORAL IMPAIRMENT IN RADIAL-ARM MAZE-LEARNING AND ACETYLCHOLINE CONTENT OF THE HIPPOCAMPUS AND CEREBRAL-CORTEX IN AGED MICE

Age-related changes in spatial learning performance were studied in relation to acetylcholine (ACh) content of brain regions in male aged (28-month-old) and young (5-month-old) mice of BDF, strain. As there were large individual differences in the spatial performance of aged mice, the aged mice were divided into two subgroups, old A and old B. The old A group included the six best performers out of the 12 aged mice and the old B group included the remaining 6 worst performers. In a radial-arm maze task with 8 baited arms, aged mice in the old B group showed a marked deficit in acquisition performance and habituation to the apparatus. In the more difficult maze task with only 4 baited arms, the aged mice in the old B group exhibited marked impairment both in working memory and reference memory throughout training, whereas the aged mice in the old A group showed deficits in reference memory during the first 20 days of training and working memory during the last 20 days relative to young mice. Neurochemical analysis revealed significant decreases in the ACh content of the hippocampus and striatum in both aged groups, and in the frontal cortex and posterior cortex of the old B group as compared to the young group. Correlational analysis showed significant correlations between learning performance in the spatial task and ACh levels in the hippocampus, frontal cortex, and posterior cortex. The present results demonstrate that a marked decrease in ACh levels in the hippocampus and cerebral cortex may be closely related to behavioral impairment in spatial learning and habituation in fully aged mice. Thus, this particular strain of mice may serve as a useful animal model for age-related impairment of cognitive functions in relation to hypofunction of the cholinergic systems in the basal forebrain.