Offline hippocampal reactivation during dentate spikes supports flexible memory

Summary Stabilizing new memories requires coordinated neuronal spiking activity during sleep. Hippocampal sharp-wave ripples (SWRs) in the Cornu Ammonis (CA) region, and dentate spikes (DSs) in the dentate gyrus (DG) are prime candidate network events supporting this offline process. SWRs have been studied extensively but the contribution of DSs remains unclear. By combining triple-(DG-CA3-CA1) ensemble recordings and closed-loop optogenetics in mice we show that, like SWRs, DSs synchronize spiking across DG and CA principal cells to reactivate population-level patterns of neuronal coactivity expressed during prior waking experience. Notably, the population coactivity structure in DSs is more diverse and higher-dimensional than that seen during SWRs. Importantly, suppressing DG granule cell spiking selectively during DSs impairs subsequent flexible memory performance in a multi-object recognition task and associated hippocampal patterns of neuronal coactivity. We conclude that DSs constitute a second offline network event central to hippocampal population dynamics serving memory-guided behavior.