학술논문

Multimodal monitoring of human cortical organoids implanted in mice reveal functional connection with visual cortex
Document Type
article
Source
Nature Communications. 13(1)
Subject
Biomedical and Clinical Sciences
Engineering
Biomedical Engineering
Neurosciences
Physical Sciences
Brain Disorders
Neurological
Humans
Animals
Mice
Neurons
Brain
Prostheses and Implants
Organoids
Visual Cortex
Language
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.