THE EFFECT OF AGE ON INTERINDIVIDUAL VARIABILITY IN MAINTENANCE AND CONTROL COMPONENTS OF RODENT WORKING MEMORY

Healthy aging is associated with declines in executive functions, including working memory (WM) and cognitive flexibility. Human studies show that aging differentially affects WM maintenance, updating, and executive control; however, these distinctions have been largely overlooked in rodent models. In this study, we investigated how aging impacts specific executive and WM subcomponents in mice. Adult and aged male C57BL/6J mice were assessed using a battery of behavioral tasks with progressively increasing executive demands, ranging from a simple delayed alternation task to cognitively flexible tasks performed in an automated operant chamber. We hypothesized that variability in age-related executive decline would be better explained by grouping animals according to the WM subcomponent most affected by aging rather than by age alone. Across tasks emphasizing WM maintenance, aged mice performed comparably to adult mice but exhibited reduced performance in tasks emphasizing WM updating and executive control. Notably, age-related interindividual variability in performance was significantly reduced by grouping mice according to task nature: mice that performed well on maintenance-focused tasks were impaired in control-demanding tasks, and vice versa. This shows that aged mice are minimally impaired in WM maintenance but strongly impaired in tasks requiring manipulation of information in WM, consistent with cognitive aging studies in humans, and that aging effects on rodent WM are subcomponent-dependent, suggesting an age-induced distinction between maintaining stable information and flexibly updating it. Collectively, these findings validate the utility of mouse models for dissecting neural mechanisms underlying age-related executive decline.