Common gene known to cause inherited autism now linked to specific behaviors

June 4, 2013

(Medical Xpress)—The genetic malady known as Fragile X syndrome is the most common cause of inherited autism and intellectual disability. Brain scientists know the gene defect that causes the syndrome and understand the damage it does in misshaping the brain's synapses—the connections between neurons. But how this abnormal shaping of synapses translates into abnormal behavior is unclear.

Now, researchers at UCLA believe they know. Using a mouse model of (FXS), they recorded the activity of networks of neurons in a living while the animal was awake and asleep. They found that during both sleep and quiet wakefulness, these showed too much activity, firing too often and in sync, much more than a normal brain.

This neuronal excitability, the researchers said, may be the basis for symptoms in children with FXS, which can include disrupted sleep, seizures or learning disabilities. The findings may lead to treatments that could quiet the excessive activity and allow for more normal behavior.

The study results are published in the June 2 online edition of the journal Nature Neuroscience.

According to the National Fragile X Foundation, approximately one in every 3,600 to 4,000 males has the disorder, as does one in 4,000 to 6,000 females. FXS is caused by a mutation in the , which encodes the fragile X mental retardation protein, or FMRP. That protein is believed to be important for the formation and regulation of synapses. Mice that lack the —and therefore lack the FMRP protein—show some of the same symptoms of human FXS, including seizures, impaired sleep, abnormal and learning defects.

"We wanted to find the link between the of synapses in the FXS mouse and the at the level of . That had not been previously established," said senior author Dr. Carlos Portera-Cailliau, an associate professor in the departments of neurology and neurobiology at UCLA. " So we tested the signaling between different neurons in Fragile X mice and indeed found there was abnormally high firing of action potentials—the signals between neurons—and also abnormally high synchrony—that is, too many neurons fired together. That's a feature that is common in early brain development, but not in the adult."

"In essence, this points to a relative immaturity of brain circuits in FXS," added Tiago Gonçalves, a former postdoctoral researcher in Portera-Cailliau's laboratory and the first author of the study.

The researchers used two-photon calcium imaging and patch-clamp electrophysiology—two sophisticated technologies that allowed them to record the signals from individual brain cells. Abnormally high firing and network synchrony, said Portera-Cailliau, is evidence of the fact that neuronal circuits are overexcitable in FXS.

"That likely leads to aberrant brain function or impairments in the normal computations of the brain," he said. "For example, high synchrony could lead to seizures; more neurons firing together could cause entire portions of the brain to fire synchronously, which is the basis of seizures."

And epilepsy, Portera-Cailliau said, is seen in up to 20 percent of children with FXS. High firing rates could also impair the ability of the brain to decode sensory stimuli by causing an overwhelming response to even simple sensory stimuli; this could lead to autism and the withdrawal from social interactions, he noted.

"Interestingly, we found that the high firing and synchrony were especially apparent at times when the animals were asleep," said Portera-Cailliau. "This is curious because a prominent symptom of FXS is disrupted sleep and frequent awakenings."

And, he noted, since sleep is important for encoding memories and consolidating learning, this hyperexcitability of brain networks in FXS may interfere with the process of laying down new memories, and perhaps explain the in children with FXS.

"Because brain scientists know a lot about the factors that regulate neuronal excitability, including inhibitory neurons, they can now try to use a variety of strategies to dampen neuronal excitation," he said. "Hopefully, this may be helpful to treat symptoms of FXS."

The next step, said Portera-Cailliau, is to explore whether Fragile X mice indeed exhibit exaggerated responses to sensory stimuli.

"An overwhelming reaction to a slight sound or caress, or hyperarousal to sensory stimuli, could be common to different types of autism and not just FXS," he said. "If hyperexcitability is the brain-network basis for these symptoms, then reducing neuronal excitability with certain drugs that modulate inhibition could be of therapeutic value in these devastating neurodevelopmental disorders."

Explore further: Neuroscientists find promise in addressing Fragile X afflictions

Related Stories

Neuroscientists find promise in addressing Fragile X afflictions

September 19, 2012
Neuroscientists at New York University have devised a method that has reduced several afflictions associated with Fragile X syndrome (FXS) in laboratory mice. Their findings, which are reported in the journal Neuron, offer ...

Fragile X syndrome can be reversed in adult mouse brain

April 11, 2012
A recent study finds that a new compound reverses many of the major symptoms associated with Fragile X syndrome (FXS), the most common form of inherited intellectual disability and a leading cause of autism. The paper, published ...

Next-generation treatments for Fragile X syndrome

November 29, 2012
A potential new therapeutic strategy for treating Fragile X syndrome is detailed in a new report appearing in the current issue of Biological Psychiatry, from researchers led by Dr. Lucia Ciranna at University of Catania ...

Most common form of inherited intellectual disability may be treatable

May 17, 2011
Advancements over the last 10 years in understanding intellectual disability (ID, formerly mental retardation), have led to the once-unimaginable possibility that ID may be treatable, a review of more than 100 studies on ...

Recommended for you

Our memory shifts into high gear when we think about raising our children, new study shows

December 15, 2017
Human memory has evolved so people better recall events encountered while they are thinking about raising their offspring, according to a new study conducted by researchers at Binghamton University, State University of New ...

Offbeat brain rhythms during sleep make older adults forget

December 15, 2017
Like swinging a tennis racket during a ball toss to serve an ace, slow and speedy brainwaves during deep sleep must sync up at exactly the right moment to hit the save button on new memories, according to new UC Berkeley ...

Study finds graspable objects grab attention more than images of objects do

December 15, 2017
Does having the potential to act upon an object have a unique influence on behavior and brain responses to the object? That is the question Jacqueline Snow, assistant professor of psychology at the University of Nevada, Reno, ...

Little understood cell helps mice see color

December 14, 2017
Researchers at the University of Colorado Anschutz Medical Campus have discovered that color vision in mice is far more complex than originally thought, opening the door to experiments that could potentially lead to new treatments ...

Scientists chart how brain signals connect to neurons

December 14, 2017
Scientists at Johns Hopkins have used supercomputers to create an atomic scale map that tracks how the signaling chemical glutamate binds to a neuron in the brain. The findings, say the scientists, shed light on the dynamic ...

Activating MSc glutamatergic neurons found to cause mice to eat less

December 13, 2017
(Medical Xpress)—A trio of researchers working at the State University of New York has found that artificially stimulating neurons that exist in the medial septal complex in mouse brains caused test mice to eat less. In ...

2 comments

Adjust slider to filter visible comments by rank

Display comments: newest first

VendicarE
5 / 5 (2) Jun 04, 2013
This is good news because Autism is known to be related to Republican disease.
Fabio P_
not rated yet Jun 04, 2013
Leave science out of petty political squabbles.

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.