What it is
The authors genetically depleted glutamatergic neurons from the neocortex and hippocampus of mice and, in newborn animals, filled the resulting cortical cavity with human stem-cell-derived cortical organoids, creating what they call xenocortical mice. The human grafts grew to occupy most of the cortical volume, produced a diversity of human cortical cell types including layer 5 extratelencephalic projection neurons, and integrated with the mouse nervous system. Calcium imaging and electrophysiology showed organized activity resembling developing circuits, and behavioural tests found broadly preserved locomotion with selective differences in limb coordination and in how spontaneous behaviour was organized.
Why it matters
Transplanting human neural organoids into rodents lets researchers study human neurodevelopment and circuit function in a living animal, but limited space and competition from host circuits have constrained how well grafts integrate, which matters for studying disease. Clearing the host cortex first gives human cortical tissue room to grow and connect, yielding circuit- and behaviour-level readouts from human neurons; the authors also used the platform to read out behaviour in a model of injury to developing human cortical cells.
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Filed underTissue Engineering and Regenerative Medicine, Bone and Dental Protein Studies, Cancer Cells and Metastasis