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See Inside Scientific American Mind Volume 24, Issue 3

Human Cells Make Mice Smarter

Implanting our larger support cells allowed the rodents' brains to work faster



FROM “FOREBRAIN ENGRAFTMENT BY HUMAN GLIAL PROGENITOR CELLS ENHANCES SYNAPTIC PLASTICITY AND LEARNING IN ADULT MICE,” BY XIAONING HAN ET AL., in CELL STEM CELL, VOL. 12. NO. 3; MARCH 7, 2013. WITH PERMISSION FROM ELSEVIER

In spring a band of brainy rodents made headlines for zipping through mazes and mastering memory tricks. Scientists credited the impressive intellectual feats to human cells transplanted into their brains shortly after birth. But the increased mental muster did not come from neurons, the lanky nerve cells that swap electrical signals and stimulate muscles. The mice benefited from human stem cells called glial progenitors, immature cells poised to become astrocytes and other glia cells, the supposed support cells of the brain.

Astrocytes are known for mopping up excess neuro-transmitters and maintaining balance in brain systems. During the past couple of decades, however, researchers started suspecting astrocytes of making more complex cognitive contributions. In the 1990s the cells got caught using calcium to accomplish a form of nonelectrical signaling. Studies since then have revealed how extensively astrocytes interact with neurons, even coordinating their activity in some cases.

Perhaps even more intriguing, our astrocytes are enormous compared with the astrocytes of other animals—20 times larger than rodent astrocytes—and they make contact with millions of neurons apiece. Neurons, on the other hand, are nearly identical in all mammals, from rodents to great apes like us. Such clues suggest astrocytes could be evolutionary contributors to our outsized intellect.

The new study, published in March in Cell Stem Cell, tested this hypothesis. A subset of the implanted human stem cells matured into rotund, humanlike astrocytes in the animals' brains, taking over operations from the native mouse astrocytes. When tested under a microscope, these human astrocytes accomplished calcium signaling at least three times faster than the mouse astrocytes did. The enhanced mice masterfully memorized new objects, swiftly learned to link certain sounds or situations to an unpleasant foot shock, and displayed un-usually savvy maze navigation—signs of mental acuity that surpassed skills exhibited by either typical mice or mice transplanted with glial progenitor cells from their own species.

Alexei Verkhratsky, a glia researcher at the University of Manchester in England who was not involved in the mouse study, calls the work “truly remarkable,” both conceptually and technically. He notes that the new results do not necessarily conflict with astrocytes' support role. Rather, Verkhratsky argues, the apparent advantages afforded by human astrocytes may be a consequence of their housekeeping abilities, underscoring the interdependence between glia and neurons.

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