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 Al Fatah Mansour, Fred H. Gage, Alysson R. Muotri, Anna Devor, Duygu Kuzum

Research output: Contribution to journalArticlepeer-review

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.

Original languageAmerican English
Article number7945
JournalNature Communications
Volume13
Issue number1
DOIs
StatePublished - 26 Dec 2022

All Science Journal Classification (ASJC) codes

  • General Chemistry
  • General Biochemistry,Genetics and Molecular Biology
  • General Physics and Astronomy

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