Brain-wide mapping reveals that engrams for a single memory are distributed across multiple brain regions

Dheeraj S. Roy, Young Gyun Park, Minyoung E. Kim, Ying Zhang, Sachie K. Ogawa, Nicholas DiNapoli, Xinyi Gu, Jae H. Cho, Heejin Choi, Lee Kamentsky, Jared Martin, Olivia Mosto, Tomomi Aida, Kwanghun Chung, Susumu Tonegawa

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50 Citations (Scopus)


Neuronal ensembles that hold specific memory (memory engrams) have been identified in the hippocampus, amygdala, or cortex. However, it has been hypothesized that engrams of a specific memory are distributed among multiple brain regions that are functionally connected, referred to as a unified engram complex. Here, we report a partial map of the engram complex for contextual fear conditioning memory by characterizing encoding activated neuronal ensembles in 247 regions using tissue phenotyping in mice. The mapping was aided by an engram index, which identified 117 cFos+ brain regions holding engrams with high probability, and brain-wide reactivation of these neuronal ensembles by recall. Optogenetic manipulation experiments revealed engram ensembles, many of which were functionally connected to hippocampal or amygdala engrams. Simultaneous chemogenetic reactivation of multiple engram ensembles conferred a greater level of memory recall than reactivation of a single engram ensemble, reflecting the natural memory recall process. Overall, our study supports the unified engram complex hypothesis for memory storage.

Original languageEnglish
Article number1799
JournalNature communications
Issue number1
Publication statusPublished - 2022 Dec

Bibliographical note

Publisher Copyright:
© 2022, The Author(s).

All Science Journal Classification (ASJC) codes

  • Physics and Astronomy(all)
  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)


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