Offline hippocampal reactivation during dentate spikes supports flexible memory

Neuron. 2024 Nov 20;112(22):3768-3781.e8. doi: 10.1016/j.neuron.2024.08.022. Epub 2024 Sep 24.

Abstract

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 for supporting this offline process. SWRs have been studied extensively, but the contribution of DSs remains unclear. By combining triple-ensemble (DG-CA3-CA1) 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 during multi-object recognition tasks 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.

Keywords: dentate spikes; hippocampus; memory consolidation; neuronal coactivity; offline reactivation; population patterns; sharp-wave ripples.

MeSH terms

  • Action Potentials* / physiology
  • Animals
  • Dentate Gyrus* / physiology
  • Hippocampus* / physiology
  • Male
  • Memory* / physiology
  • Mice
  • Mice, Inbred C57BL
  • Neurons / physiology
  • Optogenetics*