Cognitive trajectories in longitudinally trained 3xTg-AD mice

Preclinical studies in Alzheimer's disease (AD) often rely on cognitively naïve animal models in cross-sectional designs that can fail to reflect the cognitive exposures across the lifespan and heterogeneous neurobehavioral features observed in humans. To determine whether longitudinal cognitive training may affect cognitive capacities in a well-characterized AD mouse model, 3xTg and wild-type mice (n = 20) were exposed daily to a training variant of the Go-No-Go (GNG) operant task from 3 to 9 months old. At 3, 6, and 9 months, performance on a testing variant of the GNG task and anxiety-like behaviors were measured, while long-term recognition memory was also assessed at 9 months. In general, GNG training improved performance with increasing age across genotypes. At 3 months old, 3xTg mice showed slight deficits in inhibitory control that were accompanied by minor improvements in signal detection and decreased anxiety-like behavior, but these differences did not persist at 6 and 9 months old. At 9 months old, 3xTg mice displayed minor deficits in signal detection, and long-term recognition memory capacity was comparable with wild-type subjects. Our findings indicate that longitudinal cognitive training can render 3xTg mice with cognitive capacities that are on par with their wild-type counterparts, potentially reflecting functional compensation in subjects harboring AD genetic mutations.