Range of diseases may result when brain self-regulation goes awry, researchers say

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After making many thousands of measurements in experiments spanning more than 10 years, scientists at UC San Francisco have discovered that two molecular partners interact at synapses to maintain stable neuronal function. The researchers said the study could help explain how the brain is able to function efficiently and predictably over many decades, and may offer a new approach to a range of neurological and psychiatric disorders, including autism, schizophrenia, post-traumatic stress disorder, and addiction.

Every time we learn a new skill, pick up a new habit, or go through an emotional experience, our brain takes note and its circuits undergo change. But the brain’s much-heralded “plasticity” is just part of the story: if everything changed all the time, how could we maintain the memories, skills, and knowledge that make us who we are? Plasticity only has value against a predictable, stable background, and factors that threaten this stability—from genetic mutations present at birth, to life experiences such as trauma, drug abuse, and aging—have the potential to trigger brain disorders, the researchers said.

As reported September 27, 2017 in Nature, in studies of the researchers showed that when neural communication is experimentally disrupted, two proteins, called semaphorin and plexin (together dubbed “sema-plexin”), drive a compensatory reaction that rapidly restores normal function. Since fundamental aspects of in the fruit fly are shared by humans, the scientists said the newly discovered stabilization system could also act over the human lifespan to stand in opposition to any kind of mayhem in the nervous system.

“This system stabilizes neural function in response to perturbations,” said Graeme “Grae” Davis, PhD, Morris Herzstein Distinguished Professor of Medicine at UCSF and senior author of the new study. “If you disrupt this stabilizer, you’re going to be less resistant to a perturbation, whether an environmental toxin, a genetic mutation, infection or injury. So we’re imagining a totally different way of approaching diseases—lessening their severity by making the nervous system more resilient to disease-causing disruptions.”

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