Normal and slow learners: a new discriminative method based on the speed of spatial learning in aged mice

Aging is accompanied by a decline in cognitive functions, including spatial memory, yet significant variability exists in the learning abilities of older individuals. Using a large cohort of aged and young male mice, we employed spatial discrimination testing in an 8-arm radial maze to investigate age-related differences in performance in spatial learning and to categorize individual memory phenotypes within the aged population. Despite a general learning ability across groups, aged mice showed slower acquisition rates compared to young counterparts, highlighting age-related cognitive difficulties in establishing or discriminating spatial representations. By modeling individual learning curves, we classified aged mice into two subgroups-normal learners (NL) and slow learners (SL)-based on learning speed. SL mice demonstrated significantly delayed spatial memory acquisition compared to NL and young mice, suggesting pronounced heterogeneity in cognitive aging. This method provides a robust framework to explore the neurobiological underpinnings of learning deficits and may inform the development of targeted interventions to mitigate age-related memory decline.