Scientists Enhance Intelligence of Mice with Human Brain Cells

Scientists Enhance Intelligence of Mice with Human Brain Cells (io9, March 7, 2013):

It’s not quite Rise of the Planet of the Apes, but it may not be too far off, either. By grafting human glial cells into the brains of mice, neuroscientists were able to “sharply enhance” their cognitive capacities. These improvements included augmentations to memory, learning, and adaptive conditioning. It’s a breakthrough that could yield important insights into the treatment of human brain disorders.To conduct the experiment, the scientists created human chimeric mice — mice that were endowed with human glial cells.

Grafting Glia

These star-shaped cells are among the most abundant cells in the brain, performing various tasks like biochemical support of endothelial cells, supplying nutrients to nervous tissue, and repair.

But scientists have also speculated that glial cells play an important role in both our intellectual and cognitive processing capacities. And indeed, previous studies have shown that astrocytes (a type of glial cell) regulate synaptic transmission and improve the efficiency of neural circuits. This has led some neuroscientists to wonder if astrocytic evolution may be connected to the increased scope and capacity of central neural processing in humans.

To push this line of inquiry further, the University of Rochester Medical Center’s Steve Goldman, along with Maiken Nedergaard, set about the task of engineering mice with brains infused with human glial cells to see it would have any kind of influence on their cognitive capacities.Now it’s important to note that mice have glial cells, too. But they’re quite different from ours.

“Human glia are larger and have more fibers than those of lower species, and as a result each controls many more neural synapses within its geographic domain, compared to similarly situated mouse astrocytes,” Goldman told io9. “In addition, human cells may secrete higher levels of neuromodulators and cytokines that regulate synaptic activity.”

In particular, Goldman and Nedergaard identified TNFalpha, an important modulating cytokine.

And these morphological differences in glia matter; because astrocytes can both coordinate and control neural signal transmission, the researchers wanted to know if they would function differently in different species. To date, the only relevant studies have been done on rodent brains — brains with glial cells that are markedly different than our own.

So, to give mice human glia, the scientists delivered the cells into the brains of normal newborn mice.

“We did this by using a narrow glass micropipette to inject 100,000 human glial progenitor cells into each hemisphere of the developing mouse forebrain,” said Goldman. This resulted in the widespread integration of human glia into their brain. Once the mice reached adulthood, a large proportion of their forebrain glia were essentially human.To mitigate any ethical concerns, Goldman told io9 that the grafts were delivered into postnatal animals, they were of cells that could not be transmitted to offspring, and they did not involve neuronal replacement.

Improved Information Processing

Once adulthood was reached, the neuroscientists put the mice through four different cognitive tests. The results showed that the humanized mice were markedly different than their unenhanced brethren.

“The engrafted mice acquired new conditional associations and learned tasks significantly more rapidly than did their unengrafted — or mouse cell-grafted — controls,” Goldman told us.

Specifically, long-term potentiation (the increase in strength of nerve impulses along previously used pathways) was sharply enhanced in the human glial chimeric mice, as was their learning. They did a better job navigating through mazes (as per the Barnes maze navigation protocol), their object-location memory was superior, and their fear conditioning was enhanced (both for contextual situations and alarming tones).On the other hand, mice who were grafted with murine GPCs (glial cells extracted from other rodents), showed no enhancement in any of these areas.

“These findings indicate that human glia differentially enhance both activity-dependent plasticity and learning in mice,” noted the authors in the ensuing study.

This research strongly suggests that glia plays a species-specific role in species-specific intellectual and cognitive processing capabilities, a revelation that presents some interesting insights into human evolution. As a result, the researchers hope to see related studies conducted in the live adult brain.

Treating Human Brain Disorders

And indeed, in a parallel study published in Cell Stem Cell last month, Goldman’s team described how to efficiently generate glial progenitor cells from human skin cells reprogrammed into induced pluripotential cells.

“As a result, we can now establish glial progenitor cells on a patient-specific basis from individuals with brain diseases, including a number of neuropsychiatric as well as neurological disorders that appear relatively specific to humans,” Goldman told us.

Consequently, neuroscientists will now be able to determine the role that glial cells play in these disorders (including failing glial cells), and to do so in live animals. This will present a better method for evaluating potential treatments for human brain disorders.

Looking ahead, Goldman is hoping to engineer humanized mice with glial cells derived from patients with Huntington’s Disease, which will allow his team to see if there’s any connection to the cognitive deterioration in patients with that disease.

You can read the study, “Forebrain engraftment by human glial progenitor cells enhances synaptic plasticity and learning in adult mice,” in Cell Stem Cell.

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