General Cognitive /Learning Deficits in Aged Mice

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Animal research on age-related learning deficits has typically focused on the impact of age on specific learning systems. While informative, this work necessarily limits any conclusions regarding the effects of aging on general cognitive/learning abilities. This focus on specific learning systems impacts critically on our understanding of age-related deficits, given that it is estimated that 25-50% of this decline is attributable to an impairment of general cognitive ability, i.e., an ability that transcends specific learning systems or domains. The elucidation of the brain substrates for age-related cognitive deficits thus requires a conceptually-sound approach from which to parse deficits in general abilities from those which impact specific (limited) domains. Absent any attention to general influences on learning/cognitive processes, as much as 50% of decline in cognitive abilities that accrue with aging will necessarily go unexplained, mitigating the development of effective treatment strategies. Among human populations, a general influence on individuals' learning abilities reflects one of the most dominant cognitive traits ever identified. However, comparable evidence from animal subjects is sparse, and age-dependent variations in general learning factors have never been described in laboratory animals. We have recently developed a unique test battery that is sensitive to a general learning factor in mice, and this factor is psychometrically comparable to that described in humans. In Aims 1 and 2 of the present proposal, we summarize our plans to characterize the general learning/cognitive abilities of laboratory mice that range in age from young to old, and describe analysis regimens that will provide preliminary indications of the differential sources of variability that impinge on these abilities across the life span. These studies are a critical prelude to future work directed at the elucidation of the brain substrates for age-related declines in general cognitive/learning abilities.