With that in place, the researchers then started implanting human cortex organoids into the area where the mouse’s cortex was no longer developing.

Partial recovery

A bit over 85 percent of the animals that were implanted with a human organoid successfully incorporated the graft tissues. Those went on to contribute 92 percent of the cells found in the cortex of these animals. So, it wasn’t a complete replacement, but the human cells largely took over the space normally occupied by the cortex. Once there, they formed all the major types of neurons that are known to be present in the cortex. So, all that is good.

The human cells also formed some long-distance connections, as evidenced by the fact that processes from human cells were detected as far away as the spinal cord. And the neurons did engage in synchronized activity spikes, suggesting a degree of coordination.

The less good is a general lack of structure. There is some indication of local organization, in that specific cell types that form within distinct layers of a normal cortex tended to be near each other in the cortex of these animals. But there was no sign of those distinct layers being formed, suggesting that larger-scale organization is lacking.

What does this mean for the mice? Overall, it appears that having a disorganized human replacement cortex was better than having no cortex at all, but not as good as having a normally structured one.

The researchers set them loose in an area with video monitoring and then used a machine-learning classifier to group similar behavior patterns. Normal mice and the mice that had their cortex eliminated showed distinct patterns of behavior. The mice with a humanized cortex formed a third cluster, distinct from the other two. Similar things were true with body weight: mice that lacked a cortex were much lighter than normal mice, but the ones with the humanized cortex were intermediate between the two.