NREM consolidation and increased spindle counts improve age-related memory impairments and hippocampal representations

Age-related changes in sleep patterns have been linked to cognitive decline. Specifically, increasing age is associated with increasing fragmentation of sleep and wake cycles. However, it remains unknown if improvements in sleep architecture can ameliorate cellular and cognitive deficits. We evaluated how changes in sleep architecture following sleep restriction affected hippocampal representations and memory in young and old mice. After training in a hippocampus- dependent object/place recognition task, control animals were allowed to sleep ad libitum, while experimental animals underwent 5 hours of sleep restriction (SR). Interestingly, old SR mice exhibited successful object/place learning comparable to young control mice, whereas young SR and old control mice did not. Successful learning correlated with the presence of two hippocampal cell types: 1) "Context" cells, which remained stable throughout training and testing, and 2) "Object" cells, which shifted their preferred firing location when objects were introduced to the context and moved during testing. As expected, EEG analysis revealed more fragmented sleep and fewer spindles in old controls than young controls during the post-training sleep period. However, following the acute SR session, old animals exhibited increased consolidation of NREM and increased spindle count, while young mice only displayed changes in REM bout length. These results indicate that consolidation of NREM sleep and increases in spindle count serve to ameliorate age-related memory deficits and allow hippocampal representations to adapt to changing environments. eTORC BlurbAge-related cognitive decline is associated with poor sleep quality. This study shows that acute sleep restriction serves to improve memory, hippocampal representations, and sleep quality in old mice, having the opposite effect in young animals. These findings indicate that improving sleep quality may mitigate age-related cognitive decline. HighlightsAcute sleep restriction improves memory in old mice, but adversely affects young ones Acute sleep restriction makes hippocampal representations more flexible in old mice Acute sleep restriction improves sleep quality and increases spindle count in old mice Acute sleep restriction decreases hippocampal flexibility in young mice