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

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 Mansour, Fred H. Gage, Alysson R. Muotri, Anna Devor () and Duygu Kuzum ()
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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
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
Ole A. Andreassen: NORMENT Center
Abed AlFatah Mansour: The Salk Institute for Biological Studies
Fred H. Gage: The Salk Institute for Biological Studies
Alysson R. Muotri: School of Medicine
Anna Devor: Boston University
Duygu Kuzum: University of California San Diego

Nature Communications, 2022, vol. 13, issue 1, 1-15

Abstract: 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.

Date: 2022
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DOI: 10.1038/s41467-022-35536-3

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