Sleep stage-specific regulation of hippocampal activity – linked to signatures of memory processing

Abstract

Sleep is a universal behavior that has been described in a wide range of animal taxa, from flies to lizards or cetaceans. The evolution of sleep mechanisms in different animals suggests the vital importance of this state of mind, despite the risks associated with a long dissociation from the surrounding environment. In recent years, sleep has been proposed to play a central role in synaptic plasticity and in the homeostatic regulation of the neocortical and subcortical networks. Sleep seems to play two opposite and complementary roles: it promotes the downscaling of not relevant information, and it protects newly encoded and relevant information from being downscaled. In this way, the networks can still acquire new information and do not reach a saturation point. The hippocampus represents a transient station in which information coming from different associative areas is combined in one representation that, through repetitive reactivations during sleep, is sent to the neocortical areas to be integrated into long-term memory storage. For these reasons, the present work aims to describe sleep-specific changes in the neuronal dynamics of pyramidal cells in CA1, using two-photon microscopy with mice expressing a genetically encoded Ca2+ indicator (GCaMP7b). Also, considering the role of SOs and sleep spindles in consolidating hippocampus-dependent memories, the neuronal population was dissected in subgroups of cells active during slow oscillations (SOs) or sleep spindles. Our findings indicate that the global activity during SWS and REM sleep increases, in contrast to results obtained in the neocortex. On the other hand, considering sequences of SWS epochs interleaved by REM sleep, we found that the pyramidal cells, specifically active during spindles nesting in the upstate of a SO, dramatically reduced their activity. This decrease was not observed for the entire population, suggesting that REM sleep does not downregulate the activity globally, but specifically targets the networks previously involved in encoding memory information.

Die Dissertation ist gesperrt bis zum 07. März 2026 !