Orchestrated ensemble activities constitute a hippocampal memory engram

Nat Commun. 2019 Jun 14;10(1):2637. doi: 10.1038/s41467-019-10683-2.

Abstract

The brain stores and recalls memories through a set of neurons, termed engram cells. However, it is unclear how these cells are organized to constitute a corresponding memory trace. We established a unique imaging system that combines Ca2+ imaging and engram identification to extract the characteristics of engram activity by visualizing and discriminating between engram and non-engram cells. Here, we show that engram cells detected in the hippocampus display higher repetitive activity than non-engram cells during novel context learning. The total activity pattern of the engram cells during learning is stable across post-learning memory processing. Within a single engram population, we detected several sub-ensembles composed of neurons collectively activated during learning. Some sub-ensembles preferentially reappear during post-learning sleep, and these replayed sub-ensembles are more likely to be reactivated during retrieval. These results indicate that sub-ensembles represent distinct pieces of information, which are then orchestrated to constitute an entire memory.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain Mapping / methods
  • Female
  • Hippocampus / cytology
  • Hippocampus / physiology*
  • Intravital Microscopy / methods
  • Luminescent Proteins / chemistry
  • Male
  • Memory / physiology*
  • Mice, Inbred C57BL
  • Mice, Inbred ICR
  • Mice, Transgenic
  • Microscopy, Fluorescence / methods
  • Models, Animal
  • Neurons / physiology*
  • Optical Imaging / methods
  • Optogenetics / methods
  • Sleep / physiology

Substances

  • Luminescent Proteins