In research published online Thursday, August 21st in Neuron, a team of researchers at Columbia University Medical Center (CUMC), including 2010 NARSAD Distinguished Investigator Grantee Bradley S. Peterson, M.D., Ph.D., now at the Children’s Hospital Los Angeles and the University of Southern California, and four other former NARSAD Grantees, has shown that there is an over-abundance of synapses in the brains of young people with autism spectrum disorder (ASD). Synapses are necessary for brain cells to connect and communicate with each other, but too many of them may severely disrupt brain function.

In typical brain development, there is a natural “pruning” process of synapses. It has been hypothesized that this process is disrupted in people with ASD. In this new work, the researchers tested the hypothesis by examining post-mortem brains from children with and without ASD: 13 from children with ASD aged two to 9; 13 from children with ASD aged 13 to 20; and 22 from children without ASD (“controls”). The team discovered that by late childhood, synaptic density was more than 50 percent higher in those with ASD than those with typically developing brains, and sometimes as much as two-thirds greater.

“This deficit [in pruning synapses that are no longer necessary] may contribute to abnormalities in cognitive functions that humans acquire in their late childhood, teenage or early adult years, such as the acquisition of executive skill such as reasoning, motivation, judgment, language and abstract thought,” the researchers report. “Many children diagnosed with autism spectrum disorders reach adolescence and adulthood with functional disability in these skills.”

The research team then sought to understand why this happens. Working with mouse models of autism, they were able to trace the disruption of the natural synaptic pruning process to a protein called mTOR, a protein that regulates what is called “autophagy,” or cells’ ability to “self-eat,” selectively pruning those cells no longer necessary or useful.

David Sulzer, Ph.D., senior author of the study and two-time NARSAD Grantee (1989 and 1999) told The New York Times: “While people usually think of learning as requiring formation of new synapses, the removal of inappropriate synapses may be just as important.”

The researchers also found that by administering a medication that restores this natural synaptic pruning process to mice, improvements in autistic-like behaviors were observed, even when the medication was given after the behavioral symptoms had manifested.

Foundation Scientific Council Member Jeffrey Lieberman, M.D., Lawrence C. Kolb Professor and Chair of Psychiatry at CUMC and Director of the New York State Psychiatric Institute praised the study, saying, “This is an important finding that could lead to a novel and much-needed therapeutic strategy for autism.”

Read the paper abstract.

Read more about this study in the New York Times.

Read about this study in the Washington Post.