Gene Therapy Restores Youthful Neural Plasticity in the Visual Cortex

Researchers have found that manipulating levels of the Arc gene can enhance plasticity in at least the visual cortex of the mouse brain, restoring it to youthful levels in older mice. In this recent work, the researchers demonstrate this outcome via use of gene therapy. Neural plasticity is an overall measure of the degree to which brain cells can reorganize themselves, and the pace at which new cells are created to facilitate those changes. This plasticity declines with age, and the balance of evidence to date suggests that maintaining a higher level would be beneficial for many aspects of cognitive function and health of brain tissue.

Like much of the rest of the body, the brain loses flexibility with age, impacting the ability to learn, remember, and adapt. Now, scientists report they can rejuvenate the plasticity of the mouse brain, specifically in the visual cortex, increasing its ability to change in response to experience. Manipulating a single gene triggers the shift, revealing it as a potential target for new treatments that could recover the brain's youthful potential. Additional research will need to be done to determine whether plasticity in humans and mice is regulated in the same way.

The dramatic way in which the brain changes over time has long captured the imagination of scientists. A "critical window" of brain plasticity explains why certain eye conditions such as lazy eye can be corrected during early childhood but not later in life. The phenomenon has raised the questions: What ordinarily keeps the window open? And, once it's shut, can plasticity be restored? Earlier work showed that the critical window never opens in mice lacking a gene called Arc. Temporarily closing a single eye of a young mouse for a few days deprives the visual cortex of normal input, and the neurons' electrophysiological response to visual experience changes. By contrast, young mice without Arc cannot adapt to the new experience in the same way.

If there is no visual plasticity without Arc, the thinking goes, then perhaps the gene plays a role in keeping the "critical window" open. In support of the idea, the new investigation finds that in the mouse visual cortex, Arc rises and falls in parallel with visual plasticity. The two peak in teen mice and fall sharply by middle-age, suggesting they are linked. The researchers probed the connection further in two more ways. First they tested mice that have a strong supply of Arc throughout life. At middle-age, these mice responded to visual deprivation as robustly as their juvenile counterparts. By prolonging Arc's availability, the window of plasticity remained open for longer. In the second set of experiments, viruses were used to deliver Arc to middle age mice, after the critical window had closed. Following the intervention, these older mice responded to visual deprivation as a youngster would. In this case even though the window had already shut, Arc enabled it to open once again.

The prevailing notion of how plasticity declines is that as the brain develops, inhibitory neurons mature and become stronger. Increased inhibition in the brain makes it harder to express activity-dependent genes, like Arc, in response to experience or learning. That leads to decreased brain plasticity. Normally, Arc is rapidly activated in response to stimuli and is involved in shuttling neurotransmitter receptors out of synapses that neurons use to communicate with one another. Additional research will need to be done to understand precisely how manipulating Arc boosts plasticity.

Link: https://healthcare.utah.edu/publicaffairs/news/2017/08/brain-plasticity.php

Comments

It is a great day to be a mouse!

Posted by: JohnD at August 9th, 2017 6:09 PM
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