The evolution of mice and rats has been going on independently for 10-20 million years, and during this time rodents have accumulated many differences, including the brain. But that didn’t stop the authors of a new paper in the journal Cell from creating a mouse to which rat stem cells were added at the embryonic stage. They successfully took root, began working with mouse neurons, and even implicated them in brain damage.

For centuries, people have tried to create chimeras (animals made from parts of two different species) and failed every time. But modern genetic methods have made this possible. Authors of a new article in the journal Cell By combining mouse and rat cells, they managed to create a hybrid version of the brain, the most complex organ.

Two rodent species are among the animals that biologists use most in their studies. There are significant differences between them, including the structure and functioning of the brain, which is the result of millions of years of independent evolution. For example, mice are much larger and have a more sensitive sense of smell.

The authors used pluripotent stem cell transplantation, one of the most promising treatments for many diseases. At the same time, stem cell transplantation is associated with low risk and has not yet been fully studied. Therefore, biologists decided to find out how foreign cells would behave in the body of another species. For this, they used material obtained from mice and transferred into mouse embryos at an early stage of development (blastocyst).

One of the main challenges in creating a hybrid mouse and rat brain is the different developmental times of the organ in the two rodents. Indeed, the rat’s brain is larger, has a thicker cortex, and its embryogenesis lags that of the mouse by a day or two. But the experiments were successful: The mouse stem cells survived, differentiated into nerves, and mixed with the mouse’s own cells to integrate into the brain’s neural networks. At most, there were even “hybrid synapses,” contacts between neurons of two different types.

Rat cells are widely distributed throughout the hybrid brain, ranging from 0.01 percent to nearly 87 percent in different regions. But their distribution, visualized using a special fluorescent marker, turned out to be asymmetric and quite different in the left and right hemispheres.

Next, the scientists checked whether cells in the mouse could take over the work of mouse neurons. For this purpose, the olfactory regions of the mice’s brains were “turned off” or killed with a selective toxin. This precise effect did not affect the rat’s neurons. It turns out that foreign cells are good at transmitting nerve impulses. The “hybrid” mice almost completely regained their lost sense of smell: This was confirmed by a test in which they found a hidden cookie.

The new result sheds light on the behavior of stem cells from a different species in the body. It may be useful for the development of regenerative medicine and transplantology.