Parallel emergence of stable and dynamic memory engrams in the hippocampus

Nature. 2018 Jun;558(7709):292-296. doi: 10.1038/s41586-018-0191-2. Epub 2018 Jun 6.


During our daily life, we depend on memories of past experiences to plan future behaviour. These memories are represented by the activity of specific neuronal groups or 'engrams'1,2. Neuronal engrams are assembled during learning by synaptic modification, and engram reactivation represents the memorized experience 1 . Engrams of conscious memories are initially stored in the hippocampus for several days and then transferred to cortical areas 2 . In the dentate gyrus of the hippocampus, granule cells transform rich inputs from the entorhinal cortex into a sparse output, which is forwarded to the highly interconnected pyramidal cell network in hippocampal area CA3 3 . This process is thought to support pattern separation 4 (but see refs. 5,6). CA3 pyramidal neurons project to CA1, the hippocampal output region. Consistent with the idea of transient memory storage in the hippocampus, engrams in CA1 and CA2 do not stabilize over time7-10. Nevertheless, reactivation of engrams in the dentate gyrus can induce recall of artificial memories even after weeks 2 . Reconciliation of this apparent paradox will require recordings from dentate gyrus granule cells throughout learning, which has so far not been performed for more than a single day6,11,12. Here, we use chronic two-photon calcium imaging in head-fixed mice performing a multiple-day spatial memory task in a virtual environment to record neuronal activity in all major hippocampal subfields. Whereas pyramidal neurons in CA1-CA3 show precise and highly context-specific, but continuously changing, representations of the learned spatial sceneries in our behavioural paradigm, granule cells in the dentate gyrus have a spatial code that is stable over many days, with low place- or context-specificity. Our results suggest that synaptic weights along the hippocampal trisynaptic loop are constantly reassigned to support the formation of dynamic representations in downstream hippocampal areas based on a stable code provided by the dentate gyrus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium / analysis
  • Calcium Signaling
  • Dentate Gyrus / cytology
  • Dentate Gyrus / physiology
  • Hippocampus / cytology*
  • Hippocampus / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Neurons / physiology*
  • Place Cells / physiology
  • Pyramidal Cells / physiology
  • Spatial Memory / physiology*


  • Calcium