Resting after learning facilitates memory consolidation and reverses spatial reorientation impairments in female 3xTg-AD mice

BackgroundSleep is an essential component of memory consolidation and waste clearance, including pathology associated with Alzheimer's disease (AD). Facilitation of sleep decreases amyloid-β (Aβ) and tau accumulation and is important for memory consolidation.ObjectiveWe previously found that 6-month female 3xTg-AD mice were impaired at spatial reorientation learning and memory. Given the association between sleep and AD, we assessed the impact of added rest on impaired spatial reorientation that we previously observed.MethodsWe randomly assigned 3xTg-AD mice to a sleep (n = 7; 50-60 min pre- & post-task induced rest) or a non-sleep group (n = 7; remained in home cage pre- & post- task). Mice in both groups were compared to non-Tg, age-matched, non-sleep controls (n = 6). To confirm that our rest condition induced sleep, we performed the same experiment with rest sessions for both 3xTg-AD and non-Tg mice (n = 5/group) implanted with recording electrodes to capture local field potentials, which were used to classify sleep states. Markers of pathology (AT8, 6E10, M78, and M22) were also assessed in the parietal-hippocampal network, where we previously showed pTau (AT8) positive cell density predicted spatial reorientation ability.ResultsWe found that 3xTg-AD sleep mice were unimpaired at spatial reorientation compared to non-Tg mice and performed better than 3xTg-AD non-sleep mice (replicating our previous work). This recovered behavior was apparent despite no change in the density of pathology-positive cells. Further, theta-gamma coupling during sleep may explain the facilitated cognition in 3xTg-AD sleep mice, suggesting brain activity patterns during sleep may mediate the restored cognition.ConclusionsImproving sleep in early stages of AD pathology offers a promising approach for facilitating memory consolidation and improving cognition.