Structural and functional integration of human forebrain organoids with the injured adult rat visual system

Brain organoids created from human pluripotent stem cells represent a promising approach for brain repair. They acquire many structural features of the brain and raise the possibility of patient-matched repair. Whether these entities can integrate with host brain networks in the context of the injured adult mammalian brain is not well established. Here, we provide structural and functional evidence that human brain organoids successfully integrate with the adult rat visual system after transplantation into large injury cavities in the vi-sual cortex. Virus-based trans-synaptic tracing reveals a polysynaptic pathway between organoid neurons and the host retina and reciprocal connectivity between the graft and other regions of the visual system. Vi-sual stimulation of host animals elicits responses in organoid neurons, including orientation selectivity. These results demonstrate the ability of human brain organoids to adopt sophisticated function after insertion into large injury cavities, suggesting a translational strategy to restore function after cortical damage.

Automated summary

Brain organoids created from human pluripotent stem cells can integrate with the adult rat visual system after transplantation into large injury cavities, suggesting a translational strategy for restoring function after cortical damage. The study provides structural and functional evidence of the successful integration of human brain organoids with the host visual system through a polysynaptic pathway and reciprocal connectivity. Visual stimulation of the host animals elicits responses in the organoid neurons, including orientation selectivity.