Too Many Brain Connections Could be a Root Cause Behind Autism

Source: iStockphoto

By: Trenton Paul

According to a study by a team of scientists at Washington University School of Medicine in St. Louis, there is a defective gene linked to autism that affects how neurons communicate with each other in the brain.

In a series of tests performed on rodents, it was found that the gene in question resulted in too many connections being made between the neurons. This led to learning issues for the subjects, and the research team believes this finding carries over into humans as well.

Mutations in a gene linked to autism in people causes neurons to form too many connections in rodents. The findings suggest that malfunctions in communication between brain cells could be at the root of autism. Source: Getty/Washington University School of Medicine

“This study raises the possibility that there may be too many synapses in the brains of patients with autism,” said senior author Azad Bonni, MD, PhD, the Edison Professor of Neuroscience and head of the Department of Neuroscience at Washington University School of Medicine in St. Louis. “You might think that having more synapses would make the brain work better, but that doesn’t seem to be the case. An increased number of synapses creates miscommunication among neurons in the developing brain that correlates with impairments in learning, although we don’t know how.”

The genes that are linked to Autism

The neurodevelopmental disorder affects about 1 in 68 children worldwide, and its main characteristics revolve around both social and communicative challenges.

Many genes have been found to be linked to autism. Six key genes in these findings work to attach a molecular tag, called ubiquitin, to proteins. These genes, commonly referred to as ubiquitin ligases, work in the same way as a production line in a factory. They tell the larger portion of the cell what exactly it needs to do with the tagged proteins. Sometimes it tells the cell to discard them, other times it directs the cell to reroute them to another place, and the ligases even tell the cell how to increase or decrease the activity within the protein.

Those with autism often have a mutation that prevents one of the ubiquitin genes from working the way it should. The problems behind these mutations, until now, have either been poorly researched or severely misunderstood. To better understand how the system works, Bonni and his colleagues removed the ubiquitin gene RNF8 in neurons in the cerebellum of young mice. The cerebellum, which is located in the lower back of the brain just above the stem, is one of the main regions that are affected by autism.

Diagram of a brain found in young mice. Source: Rockefeller University

According to the team’s findings, neurons that lacked the RNF8 protein formed about 50 percent more synapses, which are the connections that allow neurons to send signals from one to another, than those that had the gene. The extra synapses worked, too. By measuring the electrical signal in the receiving cells, the researchers found that the strength of the signal was doubled in the mice that lacked the protein.

The synapses were essentially working overtime in the transfer process, which is thought to lead to lack of attention when a patient is placed in a learning situation. The brain is being overworked with communication, therefore it cannot absorb the learning experience.

The data collected

The mice that did not have the RNF8 protein didn’t have any obvious issues with movement, but when it came time to teach them basic motor skills (like shutting their eyes on command), they had a lot of difficulty. The team trained the mice to associate a quick puff of air to the eye with the blinking of a light. While the mice with the RFN8 protein learned to shut their eyes when they see the light blink to avoid the irritation of the coming air puff, mice without the gene shut their eyes only one-third of the time.

A neuron from the brain of young person with autism. Source: Guomei Tang and Mark S. Sonders/CUMC

There is obviously a huge difference in working with mice and children, but since these animals have been found to be very close to humans in terms of neurological makeup, these results have pushed for more research into the data collected.

“It’s possible that excessive connections between neurons contribute to autism,” Bonni said. “More work needs to be done to verify this hypothesis in people, but if that turns out to be true, then you can start looking at ways of controlling the number of synapses. It could potentially benefit not just people who have these rare mutations in ubiquitin genes but other patients with autism.”

Originally published at on November 2, 2017.