- 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
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.