THE AGED MOUSE AS A MODEL OF COGNITIVE DECLINE WITH SPECIAL EMPHASIS ON STUDIES IN NMRI MICE

The use of the aged mouse as an integrated model of age-related cognit ive decline is reviewed, with special emphasis on experiments covering the life span of NMRI mice, using different age-groups ranging from 3 through to 22 months. Age-related changes in the sensorimotor profile , spontaneous behaviour and performance in learning and memory tasks a re considered. The data provide evidence for cognitive impairment and decreases in spontaneous activity and exploration from middle age onwa rds. Chronologically, this age depends on the longevity of the strain selected; in NMRI mice, middle age corresponds to 11-12 months. Comple x learning tasks, such as the Morris water maze for spatial learning, appear to be the most sensitive to age-related changes, as are tests r equiring prolonged retention of acquired information, for example, usi ng passive avoidance. Cued and simple discrimination learning are only impaired in the oldest animals. Age-related changes in non-cognitive variables, including sensorimotor capacity, pain sensitivity, emotiona lity, or locomotor activity, do not account for the learning impairmen ts, although deficits in visual acuity cannot be excluded in the very old animals. Detailed analysis of the individual data for middle aged and old mice, using discriminant and correlation studies highlight a m arked heterogeneity between animals of any given chronological age. Fu rthermore, individual aged mice do not exhibit similar degrees of impa irment across all the behavioural variables, showing that aging is not a uniform process. The possible relationship between age-related beha vioural decline and neurochemical changes is an area as yet unexplored apart from a few isolated investigations, including a study on ChAT a nd AChE in NMRI mice. The studies in the NMRI mice illustrate the valu e of investigating the full age-range to detect an age group which sho ws cognitive decline dissociable from physical or emotional changes an d which is representative of the population as a whole.