A hippocampal circuit mechanism to balance memory reactivation during sleep

Science. 2024 Aug 16;385(6710):738-743. doi: 10.1126/science.ado5708. Epub 2024 Aug 15.

Abstract

Memory consolidation involves the synchronous reactivation of hippocampal cells active during recent experience in sleep sharp-wave ripples (SWRs). How this increase in firing rates and synchrony after learning is counterbalanced to preserve network stability is not understood. We discovered a network event generated by an intrahippocampal circuit formed by a subset of CA2 pyramidal cells to cholecystokinin-expressing (CCK+) basket cells, which fire a barrage of action potentials ("BARR") during non-rapid eye movement sleep. CA1 neurons and assemblies that increased their activity during learning were reactivated during SWRs but inhibited during BARRs. The initial increase in reactivation during SWRs returned to baseline through sleep. This trend was abolished by silencing CCK+ basket cells during BARRs, resulting in higher synchrony of CA1 assemblies and impaired memory consolidation.

MeSH terms

  • Action Potentials*
  • Animals
  • CA1 Region, Hippocampal* / physiology
  • CA2 Region, Hippocampal / physiology
  • Cholecystokinin* / metabolism
  • Interneurons / physiology
  • Learning / physiology
  • Male
  • Memory Consolidation* / physiology
  • Mice
  • Pyramidal Cells* / physiology
  • Sleep* / physiology

Substances

  • Cholecystokinin