Neuroscience: Improving human brain models

Human stem cell-derived brain-like tissue is found to integrate with the brains of newborn rats and influence behaviour, reports a Nature paper. The findings may improve our ability to produce realistic models of human neuropsychiatric diseases.

Brain organoids, made from human stem cells, represent a promising platform to model human development and disease. However, organoids grown outside of the body lack the connectivity that exists in real-life organisms, which limits their maturation and prevents them from integrating with other neuronal circuits that control behaviour. This therefore limits the ability of organoids to model genetically complex and behaviourally defined neuropsychiatric diseases. Previous research has attempted to implant human brain organoids into adult rat brains, but these cells did not mature successfully.

Sergiu Pașca and colleagues transplanted human brain organoids into the somatosensory cortex of newborn rat brains, the area responsible for receiving and processing sensory information, such as touch, from across the body. They found that the organoids matured, partially integrated into neural circuits, and demonstrated functionality in rodent brains. This integration allowed the authors to establish links between the activity of human cells and learned animal behaviour, demonstrating that the transplanted neurons could modulate rat neuronal activity and drive reward-seeking behaviour. Additionally, a group of neurons in the organoid showed activity when the authors deflected the whiskers of the rats, which indicates that the transplanted neurons can respond to sensory stimulation. The authors also found that when transplanting cells derived from three patients with Timothy syndrome — a severe genetic disease associated with heart problems — specific neuronal defects were highlighted, demonstrating the ability of this transplantation technique to reveal disease characteristics that were previously unknown.

This technique could represent a powerful resource to complement laboratory studies of human brain development and disease, the authors suggest. Future research may allow us to uncover disease characteristics in patient-derived cells that were otherwise elusive.