Functionally Distinct Neuronal Ensembles within the Memory Engram

Research output: Contribution to journalJournal articleResearchpeer-review

  • Xiaochen Sun
  • Max J Bernstein
  • Meizhen Meng
  • Siyuan Rao
  • Sørensen, Andreas Toft
  • Li Yao
  • Xiaohui Zhang
  • Polina O Anikeeva
  • Yingxi Lin

Memories are believed to be encoded by sparse ensembles of neurons in the brain. However, it remains unclear whether there is functional heterogeneity within individual memory engrams, i.e., if separate neuronal subpopulations encode distinct aspects of the memory and drive memory expression differently. Here, we show that contextual fear memory engrams in the mouse dentate gyrus contain functionally distinct neuronal ensembles, genetically defined by the Fos- or Npas4-dependent transcriptional pathways. The Fos-dependent ensemble promotes memory generalization and receives enhanced excitatory synaptic inputs from the medial entorhinal cortex, which we find itself also mediates generalization. The Npas4-dependent ensemble promotes memory discrimination and receives enhanced inhibitory drive from local cholecystokinin-expressing interneurons, the activity of which is required for discrimination. Our study provides causal evidence for functional heterogeneity within the memory engram and reveals synaptic and circuit mechanisms used by each ensemble to regulate the memory discrimination-generalization balance.

Original languageEnglish
JournalCell
Volume181
Issue number2
Pages (from-to)410-423
Number of pages14
ISSN0092-8674
DOIs
Publication statusPublished - 2020

ID: 237907793