Resting After Learning Facilitates Memory Consolidation and Reverses Spatial Reorientation Impairments in ‘New Surroundings’ in 3xTg-AD Mice

Sleep is an essential component of productive memory consolidation and waste clearance, including pathology associated with Alzheimer's disease (AD). Facilitation of sleep decreases Aβ and tau accumulation and is important for the consolidation of spatial memories. We previously found that 6-month female 3xTg-AD mice were impaired at spatial reorientation. Given the association between sleep and AD, we assessed the impact of added rest on impaired spatial reorientation that we previously observed. We randomly assigned 3xTg-AD mice to a rest (n=7; 50 min pre- & post-task induced rest) or a non-rest group (n=7; mice remained in the home cage pre- & post-task). Mice in both groups were compared to non-Tg, age-matched, non-rest controls (n=6). To confirm that our sleep condition induced sleep, we performed the same experiment with rest sessions for both 3xTg-AD and non-Tg mice (n=6/group) implanted with recording electrodes to capture local field potentials (LFPs), which were used to classify sleep states. Markers of pathology were also assessed in the parietal-hippocampal network, where we previously showed pTau positive cell density predicted spatial reorientation ability (pTau, 6E10, M78, and M22). However, we found that 3xTg-AD rest mice were not impaired at spatial reorientation compared to non-Tg mice and performed better than 3xTg-AD non-rest mice (replicating our previous work). This recovered behavior persisted despite no change in the density of pathology positive cells. Thus, improving sleep in early stages of AD pathology offers a promising approach for facilitating memory consolidation and improving cognition.