Contextual Fear Memory Retrieval Is Vulnerable to Hippocampal Noise

Cereb Cortex. 2021 Jan 5;31(2):785-794. doi: 10.1093/cercor/bhaa257.


Memory retrieval depends on reactivation of memory engram cells. Inadvertent activation of these cells is expected to cause memory-retrieval failure, but little is known about how noisy activity of memory-irrelevant neurons impacts mnemonic processes. Here, we report that optogenetic nonselective activation of only tens of hippocampal CA1 cells (∼0.01% of the total cells in the CA1 pyramidal cell layer) impairs contextual fear memory recall. Memory recall failure was associated with altered neuronal reactivation in the basolateral amygdala. These results indicate that hippocampal memory retrieval requires strictly regulated activation of a specific neuron ensemble and is easily disrupted by the introduction of noisy CA1 activity, suggesting that reactivating memory engram cells as well as silencing memory-irrelevant neurons are both crucial for memory retrieval.

Keywords: Arc; amygdala; hippocampus; memory; optogenetics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Basolateral Nuclear Complex / physiology
  • CA1 Region, Hippocampal / cytology
  • CA1 Region, Hippocampal / physiology
  • Conditioning, Psychological
  • Cytoskeletal Proteins / genetics
  • Cytoskeletal Proteins / metabolism
  • Fear / psychology*
  • Hippocampus / cytology
  • Hippocampus / physiology*
  • Male
  • Mental Recall / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • Neurons / physiology


  • Cytoskeletal Proteins
  • Nerve Tissue Proteins
  • activity regulated cytoskeletal-associated protein