Embryonic neurons transplanted into mice can induce a period of flexibility in a relatively rigid older brain, suggesting a possible mechanism to repair damaged brain circuits, according a study published this week in Science.

Inhibitory neurons transplanted from the embryonic brain into the postnatal brain Image: Derek Southwell

"It's terrific," said neuroscientist Takao Hensch of Harvard University, who was not involved in the research. "This is a very nice demonstration that just transplanting those very cells that [influence brain development] initially can reintroduce a period of plasticity. The obvious therapeutic implications are very exciting."

As a young brain matures, it goes through various periods of reorganization known as critical periods -- short bursts of neural plasticity. The development of the visual system, for example, involves a period of brain plasticity shortly after birth in which neurons are rewired to "match up the connections in the visual cortex so that the world looks the same whether you're seeing it through the left eye or the right eye," explained neurobiologist and study author Michael Stryker of the University of California, San Francisco.

During this period, if one eye is blurred or occluded, it becomes largely disconnected from the visual cortex, and those neurons become rewired to receive information from the working eye -- a phenomenon known as ocular dominance plasticity. Thus, even if the occluded eye regained function later in life, the individual would not be able to properly see with it.

About 10 years ago, scientists, including Hensch, discovered that inhibitory neurons -- neurons that decrease the firing rate of the other neurons to which they are connected -- are "needed to orchestrate the plasticity," Hensch said. Mice with a genetic mutation that resulted in inadequate inhibition never had a critical period, but it could be rescued by a drug that increases inhibition. Furthermore, enhancing inhibition prior to the normal critical period resulted in an early period of plasticity. Enhancing inhibition after the critical period occurred, however, did not result in a second period of plasticity.

Now, using this same system as a model to study the mechanisms underlying this critical period, Stryker and his colleagues successfully induced a second critical period several days after the normal one had ended. When inhibitory neuron precursors from the brains of embryonic mice were transplanted into the brain of neonatal and young mice, the precursors integrated into the visual cortex, developed into mature inhibitory neurons, and enabled the brain to compensate for a loss of sensory input from one eye, similar to how it would during the natural critical period.

Interestingly, this second period occurred when the transplanted neurons were precisely the age they would be during the peak of the natural critical period for ocular dominance, Stryker noted. A week earlier or a week later, and the effect was much less pronounced.

"It seems likely to us that something else about these developing inhibitory neurons, something more than just the inhibitory neurotransmitters they provide, is important for causing plasticity," Stryker said. Although the researchers do not yet understand exactly what that "something else" is, he said, "we think it has enormous promise because it shows the capacity of these young neurons to induce a new state of plasticity in an older brain, which we hope will be very useful in recovering from brain injury."

Future studies should delve further into the changes induced by the transplantations, Hensch said, including the precise neural connections that are formed or lost, how long the effects last, and whether or not there are functional implications. For example, how would such transplants affect an animal that has permanently lost its vision in one eye due to its occlusion during the natural critical period? Hensch wondered. "If you could take such an animal and then transplant these cells in adulthood, reinduce the plasticity, and rescue function, that would be a big step towards therapeutic applications."


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