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- Title
Multimodal monitoring of human cortical organoids implanted in mice reveal functional connection with visual cortex.
- Authors
Wilson, Madison N.; Thunemann, Martin; Liu, Xin; Lu, Yichen; Puppo, Francesca; Adams, Jason W.; Kim, Jeong-Hoon; Ramezani, Mehrdad; Pizzo, Donald P.; Djurovic, Srdjan; Andreassen, Ole A.; Mansour, Abed AlFatah; Gage, Fred H.; Muotri, Alysson R.; Devor, Anna; Kuzum, Duygu
- 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. Neuronal organoids derived from human induced pluripotent stem cells can be transplanted and integrated into the rodent cortex for the study of brain development and function. Here the authors demonstrate use of transparent graphene microelectrodes and two photon imaging for longitudinal, multimodal monitoring of functional connectivity between human iPSC derived neuronal organoids and the mouse cortex.
- Subjects
PLURIPOTENT stem cells; VISUAL cortex; INDUCED pluripotent stem cells; ORGANOIDS; CINGULATE cortex; VISUAL perception; NEURAL circuitry
- Publication
Nature Communications, 2022, Vol 13, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-022-35536-3