Researchers from Yale University identified common neural circuits affected by autism-risk genes. They also identified when, where, and in what cell types those genes exert their effects on the developing human brain and lead to autism spectrum disorders.

Although other genes and neural circuits that contribute to autism spectrum still remain to be found, the findings suggest new targeted treatments for autism may be possible, said Nenad Sestan, professor of neurobiology, investigator for Kavli Institute for Neuroscience at Yale, and co-senior author of the paper.

"We know now that we may not have to treat the whole brain, that changes related to mutations in autism-risk genes may affect particular neural circuits at specific places at specific times," Sestan said.

The Yale team led by Sestan and Matthew State, now at the University of California-San Francisco, together with James Noonan of Yale School of Medicine, Bernie Devlin of the University of Pittsburgh, and Kathryn Roeder of Carnegie-Mellon University searched for molecular crossroads shared by nine genes conclusively linked to autism.

An analysis of when and where nine of those autism genes are most co-activated identified at least two such molecular crossroads.

The first influence a specific cell type — excitatory projection neurons — and their neural circuits, which form and become active about three to five months after conception.

The second implicates the mid-foetal frontal cortex, a brain region critical for cognition, language, and complex motor behaviours.

It is unclear exactly how these mechanisms might lead to symptoms of autism, the authors noted.     It could be that several developmental changes could influence how the disorders develop in the same way that hypertension contributes to both heart attack and stroke, they said.

"The brain is extraordinarily complicated, but this approach gives us a way to pinpoint some of the mechanisms that contribute to a host of complex brain disorders," Sestan said. The study was published in the journal Cell.

(Agencies)

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