Abstract
Age-related changes in sleep patterns have been linked to cognitive decline. Specifically, age is associated with increased fragmentation of sleep and wake cycles. Yet 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. Following training in a hippocampus-dependent object/place recognition task, control animals were allowed to sleep normally, while experimental animals underwent 5 hr of sleep restriction (SR). Interestingly, old SR mice exhibited proper object/place memory, similarly to young control mice, whereas young SR and old control mice did not. Successful memory 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 initial spindles in old controls than young controls during the post-training sleep period. However, following the acute SR session old animals displayed more consolidate NREM and increased spindle count, while young mice did not significantly display changes in sleep architecture. These results indicate that consolidation of NREM sleep and increases in spindle numbers serve to ameliorate age-related memory deficits and allow hippocampal representations to adapt to changing environments.
Significance Statement Age-related cognitive decline is associated with poor sleep quality. Interestingly, while sleep restriction has strong negative effects in young subjects, it does not affect or leads to performance improvements in old ones. This study investigated the possibility that sleep restriction differentially affected sleep architecture in young and old mice, leading to distinct cellular and cognitive phenotypes. In young animals, sleep restriction produced memory impairments and less flexible hippocampal representations, without significantly affecting sleep quality. However, in old animals, it led to improved sleep quality, enhanced memory, and more precise and flexible hippocampal representations. These findings have important implications because they indicate that the risk factors associated with poor sleep quality and age-related cognitive decline can be modifiable.