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

• DOI: 10.1038/s41467-022-35536-3
• Publication Date: 2022-12-26T12:03:16Z
• Authors: 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; Duygu Kuzum
• Keywords: Organoid; Cortical neurons

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