Scientists Inject Human Brain Cells Into Mice, Make Them Smarter

And you thought it was all about the neurons.

In an experiment that might seem like something only a mad scientist would conjure, researchers injected human brain cells into the brains of mice to see how it would affect the way the mice thought. It did: the mice got smarter. But the cognition boosting cells weren’t neurons, they were the red-headed step-children of neuroscience called astrocytes. The study turns on its head the role historically attributed to astrocytes of simply supporting the all important function of neurons without playing a significant role in how we learn and think. It may very well be that humans owe much of their unique cognitive capabilities to astrocytes.

When the German pathologist Rudolf Virchow first visualized them through a microscope in 1846 he called them ‘glia,’ the Greek word for glue, because the cells seemed to only fill in the space between the brain’s neurons. Subsequent study over the next century and a half only served to confirm the idea that these glial cells were only important insofar as they supported the function of neurons. The glial cells in the brain – called astrocytes for their numerous processes which project outward in star-like radiance – make sure the fluid surrounding neurons has the right concentration of ions and other molecules, and is clear of molecular waste. But research has emerged over the past few decades that suggest astrocytes might play more than a housekeeping role in the brain and may actually be important for cognitive function.

If it’s true that astrocytes help us to think, and human’s are the smartest of all thinkers, then maybe we owe much of our cognitive prowess to astrocytes. To test this idea, scientists at University of Rochester Medical Center injected human glial progenitor cells into the brains of mice and tested to see if it changed the mice’s ability to remember and learn. Glial progenitors are precursor cells that mature into astrocytes in the young brain. The human progenitors were injected into the brains of mice shortly after they were born. In an early show of superiority, the human progenitors drove out the mice’s own progenitors. By the time the mice were six months old, most of their astrocytes were of human origin.

The researchers then subjected their “human glial chimeric” mice to tests to see if the human astrocytes affected their memory and learning capabilities. To make sure any differences were specifically due to the human astrocytes and not just more astrocytes, the performance of the chimeric mice was compared to others which had received injections of mouse astrocytes.

In both the ability to learn their way around a maze and to associate a tone with a foot shock – that is, to learn to be afraid of the tone – the mice with human astrocytes outperformed their mouse cell only competitors. The tone-shock test was particularly impressive. While the mice receiving mouse astrocytes require several trials to learn to be afraid of the tone, those with human astrocytes became fearful after a single shock.

In an attempt to explain how the human astrocytes could enhance cognitive abilities, the researchers took a look at how mice neurons behave in the presence of the foreign cells. Long-term potentiation (LTP) is a phenomenon in which the response of a neuron to a signal is boosted after it receives a strong stimulus. Neuroscientists believe that LTP is at the core of learning and memory, that the boosted responses are what memories look like at the level of single neurons. The neurons surrounded by human astrocytes in the chimeric mice showed more pronounced LTP than those with mice astrocytes.

The human astrocytes were also seen to communicate with each other (by propagating calcium waves) much more quickly than mice astrocytes communicated. So, together with the LTP boost that could explain the chimera’s ability to learn, human astrocytes could also communicate with each other and with neurons more quickly.

The study appeared in a recent article of Cell Stem Cell.

Steven Goldman, co-senior author of the study, thinks it is the coordination between neurons and astrocytes that sets humans apart. “In a fundamental sense we are different from lower species,” he said in a press release. “Our advanced cognitive processing capabilities exist not only because of the size and complexity of our neural networks, but also because of the increase in functional capabilities and coordination afforded by human glia.”

Bruce Ransom, a neuroscientist at the University of Washington who was not involved in the study, put the results in a broader context in a conversation with ScienceNews. “It’s a stunning result. It provides the first unequivocal evidence that astrocytes may well have been one of the evolutionary drivers of human capabilities.”

When Einstein died, scientists raced to find something about his brain that explained his extraordinary intellect. It turned out to be smaller than the average brain, not larger, but with perhaps some extra convolutions in an area of the prefrontal cortex important for abstract thought. Another difference, they found, was that the relative proportion of astrocytes was higher in Einstein’s brain compared to the rest of the population. They didn’t know what to make if it back in the eighties when the discovery was made. Now, this long underestimated cell could finally be given its due appreciation.