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

Author

Listed:
  • Dheeraj S. Roy

    (Massachusetts Institute of Technology
    Broad Institute of MIT and Harvard)

  • Young-Gyun Park

    (Massachusetts Institute of Technology
    Korea Advanced Institute of Science and Technology (KAIST))

  • Minyoung E. Kim

    (Massachusetts Institute of Technology)

  • Ying Zhang

    (Massachusetts Institute of Technology)

  • Sachie K. Ogawa

    (Massachusetts Institute of Technology
    University of Texas Southwestern Medical Center)

  • Nicholas DiNapoli

    (Massachusetts Institute of Technology)

  • Xinyi Gu

    (Massachusetts Institute of Technology)

  • Jae H. Cho

    (Massachusetts Institute of Technology)

  • Heejin Choi

    (Massachusetts Institute of Technology)

  • Lee Kamentsky

    (Massachusetts Institute of Technology)

  • Jared Martin

    (Massachusetts Institute of Technology)

  • Olivia Mosto

    (Massachusetts Institute of Technology)

  • Tomomi Aida

    (Massachusetts Institute of Technology)

  • Kwanghun Chung

    (Broad Institute of MIT and Harvard
    Massachusetts Institute of Technology
    Yonsei University)

  • Susumu Tonegawa

    (Massachusetts Institute of Technology
    Massachusetts Institute of Technology)

Abstract

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.

Suggested Citation

  • 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 , 2022. "Brain-wide mapping reveals that engrams for a single memory are distributed across multiple brain regions," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
  • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-29384-4
    DOI: 10.1038/s41467-022-29384-4
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    References listed on IDEAS

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    2. Xunda Wang & Alex T. L. Leong & Shawn Z. K. Tan & Eddie C. Wong & Yilong Liu & Lee-Wei Lim & Ed X. Wu, 2023. "Functional MRI reveals brain-wide actions of thalamically-initiated oscillatory activities on associative memory consolidation," Nature Communications, Nature, vol. 14(1), pages 1-21, December.
    3. Gianluca Milano & Alessandro Cultrera & Luca Boarino & Luca Callegaro & Carlo Ricciardi, 2023. "Tomography of memory engrams in self-organizing nanowire connectomes," Nature Communications, Nature, vol. 14(1), pages 1-11, December.
    4. Ruijie Li & Junjie Huang & Longhui Li & Zhikai Zhao & Susu Liang & Shanshan Liang & Meng Wang & Xiang Liao & Jing Lyu & Zhenqiao Zhou & Sibo Wang & Wenjun Jin & Haiyang Chen & Damaris Holder & Hongban, 2023. "Holistic bursting cells store long-term memory in auditory cortex," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    5. Yann Vanrobaeys & Utsav Mukherjee & Lucy Langmack & Stacy E. Beyer & Ethan Bahl & Li-Chun Lin & Jacob J. Michaelson & Ted Abel & Snehajyoti Chatterjee, 2023. "Mapping the spatial transcriptomic signature of the hippocampus during memory consolidation," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    6. Qi Wang & Jia-Jie Zhu & Lizhao Wang & Yan-Peng Kan & Yan-Mei Liu & Yan-Jiao Wu & Xue Gu & Xin Yi & Ze-Jie Lin & Qin Wang & Jian-Fei Lu & Qin Jiang & Ying Li & Ming-Gang Liu & Nan-Jie Xu & Michael X. Z, 2022. "Insular cortical circuits as an executive gateway to decipher threat or extinction memory via distinct subcortical pathways," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    7. Stephanie L. Grella & Amanda H. Fortin & Evan Ruesch & John H. Bladon & Leanna F. Reynolds & Abby Gross & Monika Shpokayte & Christine Cincotta & Yosif Zaki & Steve Ramirez, 2022. "Reactivating hippocampal-mediated memories during reconsolidation to disrupt fear," Nature Communications, Nature, vol. 13(1), pages 1-19, December.

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