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Multimodal monitoring of human cortical organoids implanted in mice reveal functional connection with visual cortex

Author

Listed:
  • Madison N. Wilson

    (University of California San Diego)

  • Martin Thunemann

    (Boston University)

  • Xin Liu

    (University of California San Diego)

  • Yichen Lu

    (University of California San Diego)

  • Francesca Puppo

    (School of Medicine)

  • Jason W. Adams

    (School of Medicine
    University of California San Diego, School of Medicine)

  • Jeong-Hoon Kim

    (University of California San Diego)

  • Mehrdad Ramezani

    (University of California San Diego)

  • Donald P. Pizzo

    (University of California San Diego)

  • Srdjan Djurovic

    (Oslo University Hospital
    NORMENT Center
    University of Bergen
    University of Oslo)

  • Ole A. Andreassen

    (NORMENT Center
    University of Oslo
    Oslo University Hospital
    University of Oslo)

  • Abed AlFatah Mansour

    (The Salk Institute for Biological Studies
    The Hebrew University of Jerusalem)

  • Fred H. Gage

    (The Salk Institute for Biological Studies)

  • Alysson R. Muotri

    (School of Medicine
    University of California San Diego, School of Medicine
    University of California San Diego
    University of California San Diego)

  • Anna Devor

    (Boston University
    Massachusetts General Hospital)

  • Duygu Kuzum

    (University of California San Diego)

Abstract

Human cortical organoids, three-dimensional neuronal cultures, are emerging as powerful tools to study brain development and dysfunction. However, whether organoids can functionally connect to a sensory network in vivo has yet to be demonstrated. Here, we combine transparent microelectrode arrays and two-photon imaging for longitudinal, multimodal monitoring of human cortical organoids transplanted into the retrosplenial cortex of adult mice. Two-photon imaging shows vascularization of the transplanted organoid. Visual stimuli evoke electrophysiological responses in the organoid, matching the responses from the surrounding cortex. Increases in multi-unit activity (MUA) and gamma power and phase locking of stimulus-evoked MUA with slow oscillations indicate functional integration between the organoid and the host brain. Immunostaining confirms the presence of human-mouse synapses. Implantation of transparent microelectrodes with organoids serves as a versatile in vivo platform for comprehensive evaluation of the development, maturation, and functional integration of human neuronal networks within the mouse brain.

Suggested Citation

  • Madison N. Wilson & Martin Thunemann & Xin Liu & Yichen Lu & Francesca Puppo & Jason W. Adams & Jeong-Hoon Kim & Mehrdad Ramezani & Donald P. Pizzo & Srdjan Djurovic & Ole A. Andreassen & Abed AlFatah, 2022. "Multimodal monitoring of human cortical organoids implanted in mice reveal functional connection with visual cortex," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-35536-3
    DOI: 10.1038/s41467-022-35536-3
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    References listed on IDEAS

    as
    1. Giorgia Quadrato & Tuan Nguyen & Evan Z. Macosko & John L. Sherwood & Sung Min Yang & Daniel R. Berger & Natalie Maria & Jorg Scholvin & Melissa Goldman & Justin P. Kinney & Edward S. Boyden & Jeff W., 2017. "Cell diversity and network dynamics in photosensitive human brain organoids," Nature, Nature, vol. 545(7652), pages 48-53, May.
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    Cited by:

    1. Harman Ghuman & Kyungsoo Kim & Sapeeda Barati & Karunesh Ganguly, 2023. "Emergence of task-related spatiotemporal population dynamics in transplanted neurons," Nature Communications, Nature, vol. 14(1), pages 1-15, December.

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