Overexcited Brain Cells May Spur Symptoms of Autism, Stanford Study Finds

By Robert Langreth - Jul 27, 2011 10:00 AM PT

Stimulating brain cells with light can generate autism-like symptoms, Stanford University researchers reported in a mouse study that may provide clues on what causes the disease in people.

The scientists implanted light-sensitive proteins into parts of the brain linked to social behavior in normal mice, and then activated them with blue lasers routed into the brain using fiber-optic cables. Normally gregarious mice didn't socialize with other animals and developed a brain-wave pattern seen in some people with autism and schizophrenia. Their interest in exploring inanimate objects was normal, according to the results published online in the journal Nature.

The findings provide evidence for the theory that autism and brain disorders such as schizophrenia, where social behavior breaks down, may be caused by brain circuits oversensitive to stimulation, the researchers said.

“It definitely provides an insight into what might be wrong in autism, which is a huge step,” said Karl Deisseroth, a Stanford University psychiatrist and senior author, in a telephone interview. “It opens the door to a whole host” of treatment possibilities, including use of drugs or devices that calm or shield specific parts of the brain.

In a 2009 study, the U.S. Centers for Disease Control and Prevention estimated that about 1 in 110 American children have autism or other autism spectrum disorders. Symptoms, including impaired development of social and communication skills, appear by age three, according to the National Institutes of Health. While the disorder’s causes aren’t understood, genetics have been found to play a role.

Signaling Theory
Some neurons in the brain spur signaling between cells when excited, and others act to calm down the signaling. One theory is that the balance between the two between may be disrupted in autism, Deisseroth said. This idea is supported by the fact that some genes linked to rare forms of autism appear to promote excitation of brain cells, he said.

“If a cell is always on, it can’t communicate much information,” Deisseroth said. “As a result, the animals cannot handle the complexity of the social interaction.”

Mice normally are social creatures that would spend “many minutes” investigating, sniffing, and interacting with a new mouse of the same sex that is placed in the cage, Deisseroth said. This behavior disappeared in mice after the lasers were shined on certain cells.

Restored Behavior
When the researchers used the laser to activate different cells that inhibit brain activity, the social behavior was partly restored, Deisseroth said.

Until Deisseroth and colleagues at Humboldt University in Berlin, Germany and Weizmann Institute of Science in Rehovot, Israel completed the research, the excitation theory had been “impossible to test because there is no way to reach into a functioning mammalian brain and selectively boost excitability,” he said. That’s now been overcome, he said.

The finding “has broad implications across many different therapeutic areas,” said Robert H. Ring, vice president of translational research at Autism Speaks, an advocacy group, and former head of autism research at Pfizer Inc. (PFE) “It opens up avenues of research that may ultimately allow us to be very specific on how we develop therapies” for autism and other brain disorders with deficits in social behavior.

Ring predicted Deisseroth’s laser method would be “revolutionary” in helping discover the causes of brain disorders on a molecular level, though therapies based on the technique are much farther off.

To contact the reporter on this story: Robert Langreth in New York at rlangreth@bloomberg.net