The ability to store and retrieve learned information over prolonged periods of time is an essential and intriguing property of the brain. Insight into the neurobiological mechanisms that underlie memory consolidation is of utmost importance for our understanding of memory persistence and how this is affected in memory disorders. Recent evidence indicates that a given memory is encoded by sparsely distributed neurons that become highly activated during learning, so-called engram cells. Research by us and others confirms the persistent nature of cortical engram cells by showing that these neurons are required for memory expression up to at least 1 month after they were activated during learning. Strengthened synaptic connectivity between engram cells is thought to ensure reactivation of the engram cell network during retrieval. However, given the continuous integration of new information into existing neuronal circuits and the relatively rapid turnover rate of synaptic proteins, it is unclear whether a lasting learning-induced increase in synaptic connectivity is mediated by stable synapses or by continuous dynamic turnover of synapses of the engram cell network. Here, we first discuss evidence for the persistence of engram cells and memory-relevant adaptations in synaptic plasticity, and then propose models of synaptic adaptations and molecular mechanisms that may support memory persistence through the maintenance of enhanced synaptic connectivity within an engram cell network.

Original languageEnglish
Article number661476
Pages (from-to)1-15
Number of pages15
JournalFrontiers in Synaptic Neuroscience
Publication statusPublished - 24 Mar 2021

Bibliographical note

Funding Information:
Funding. This study was funded by an NWO VIDI grant (016.168.313) to MO, EV, and MM and NWO Veni grant (016.171.033) to PR-R.

Publisher Copyright:
© Copyright © 2021 Rao-Ruiz, Visser, Mitrić, Smit and van den Oever.

Copyright 2021 Elsevier B.V., All rights reserved.


  • cellular feedback loops
  • engram cell network
  • memory engram
  • memory persistence
  • synaptic connectivity


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