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GENEVA – For a long time, the brain was considered a kind of black box, whose internal workings were largely a mystery. But recently, this special organ has started yielding its secrets, thanks in part to the progress made in the field of genetics.

Neuroscientists from the University of Geneva have achieved a breakthrough that could open great medical perspectives in “fixing” damaged brains. The researchers opened the cranium of mice – which remained alive throughout – and “reprogrammed” some of its brain's neurons. In other words, they changed the original function of the mice’s brain cells!

Denis Jabaudon and his colleagues -- who detailed their research earlier this year in Nature Neuroscience monthly -- studied the cerebral cortex, the grey matter that “constitutes the human’s most evolved structure compared to the other mammals, and allows us to use speech and make sharp analyses.”

We have known for several decades that the cerebral cortex has six different layers, each with its own specialized neurons. “Among those, the thalamorecipient neurons are the first to receive sensory signals from the outside,” explains Jabaudon. “In another layer, you can find the corticospinal neurons responsible for motor output, and connecting the cortex with the spinal cord.” Keeping the black box metaphor, the first are the entrance and the other, the exit door.

Holy grail

Neuroscientists know that a gene called Fezf2 plays a crucial part in the formation of corticospinal neurons. From there, it was “only” a matter of incorporating the Fezf2 into the mice’s thalamorecipients, after their progenitor cells finished dividing in order to constitute the adult organ, to eventually watch those cells mutate into cortico-spinal neurons. “We basically turned the entrance door into an exit door!”

Zoltan Molnar, professor in developmental neurosciences at Oxford University, who didn’t contribute to the experiment, believes the research is momentous. “This is the first time such a result is obtained in vivo, on cells no longer in their dividing process. And it’s fantastic,” he said. "The next step would be to try and apply the same method to superior stages.”

Jabaudon confirmed that his team used newborn mice, since their cortex is more flexible than an adult’s. As a matter of fact, the two types of neurons implicated in the metamorphosis are basically “cousins”, genetically speaking. The most important feature was to be sure the final neurons weren’t hybrids that would play both their original and newly implemented roles. "There was a complete transformation of their capacities,” Jabaudon says.

The potential applications for this research are many: “It may become possible, at some point, to reprogram people’s cortico-spinal neurons where they have become inefficient," he says. "Typical patients would include those affected by amyotrophic lateral sclerosis. (ALS)” This neuro-degenerative disease, which struck American baseball player Lou Gehrig and British astrophysicist Stephen Hawking, progressively paralyses the whole muscular system from the limbs to the trunk of the body.

The Geneva researcher admits that “the Holy Grail would be to carry out this experiment on the neurons of a completely grown up organism.”

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