Children and adolescents with autism were found to have a surplus of synapses in the brain, most likely due to a slowdown in the "pruning " process of development.

Synapses are the points at which neurons connect and communicate; excess synapses could have a significant effect on how the brain functions, Columbia University Medical Center reported.  A drug that restores normal synaptic pruning could improve autistic-like behavior in mice.

"This is an important finding that could lead to a novel and much-needed therapeutic strategy for autism," said Jeffrey Lieberman, MD, Lawrence C. Kolb Professor and Chair of Psychiatry at CUMC and director of New York State Psychiatric Institute, who was not involved in the study.

In normal brain development a burst of synapse formation occurs in infancy, but pruning eliminates about half of these cortical synapses. Synapses are highly affected by a number of genes linked to autism.

To make their findings the researchers brains children who had autism and but had died from other causes.  They also looked at control brains of healthy children who had died. The team measured the synapse density in small sample of each brain by counting the number of spines that branch from the cortical neurons. The team found that by late childhood the spine density had dropped in about half of the brains of healthy individuals and only about 16 percent of those with autism.

"It's the first time that anyone has looked for, and seen, a lack of pruning during development of children with autism," said David Sulzer, PhD, professor of neurobiology in the Departments of Psychiatry, Neurology, and Pharmacology at CUMC. "Although lower numbers of synapses in some brain areas have been detected in brains from older patients and in mice with autistic-like behaviors."

Using autistic mouse models the team traced the pruning effect to a protein called mTOR, which when overactive can cause brain cells to lose much of their "self eating" (autophagy) ability.

"While people usually think of learning as requiring formation of new synapses, "Dr. Sulzer says, "the removal of inappropriate synapses may be just as important."

The team found they could restore autophagy and synaptic pruning by administering the drug rapamycin, which inhibits mTOR; this reversed some of the autistic symptoms in mice. 

The findings were published Aug. 21 online issue of the journal Neuron.