Animal models can't 'tune out' stimuli, mimicking sensory hypersensitivity in humans

June 12, 2017, University of California, Los Angeles
UCLA researchers Cynthia X. He and Carlos Portera-Cailliau discuss their findings. Credit: UCLA

By tickling the whiskers of mice, and recording how they respond, UCLA researchers may be closer to understanding why many children with autism cover their ears when they hear loud sounds or can't tolerate scratchy wool sweaters.

Scientists report in the June 12 issue of the Journal of Neuroscience that mice genetically engineered to mimic a type of in humans, fragile X syndrome, are unable to adapt to, or tune out, repeated stimulation to their whiskers—unlike ordinary mice. The findings have implications for a common symptom—sensory hypersensitivity—in humans with autism.

"If we can understand more about this mechanism, or help push the brain in the direction of adaptation, we could really help children with autism," said Dr. Carlos Portera-Cailliau, professor of neurology and neurobiology at the David Geffen School of Medicine at UCLA and the paper's senior author. "Currently, their brains do not mature in a way that allows this adaptation mechanism to work properly."

Hypersensitivity to touch, sounds, taste and other sensory input is a central feature of autism, a disorder characterized by social interaction difficulties, repetitive behaviors and language impairment. Sensory hypersensitivity that leads to avoidance, or "tactile defensiveness," is important to understand because it contributes to other characteristics of autism such as anxiety, sleep disturbances and inattention.

To learn more, Portera-Cailliau and his colleagues used a genetic mouse model of fragile X syndrome, the most common genetic cause of autism and learning disabilities in humans, to determine whether mice with fragile X syndrome show the same "tactile defensiveness" seen in people with autism. The scientists studied the behavior of 14-day-old mice and running on a ball as a wire comb repeatedly touched their whiskers. The neurological development of a 14-day-old mouse roughly corresponds to the months immediately before and after birth in humans—a time when experiences shape the brain circuits involved in processing .

Two-photon calcium imaging captured mouse neurons firing in response to whisker tweaks. Credit: Portera-Cailiau Lab/UCLA

The researchers found that the young fragile X mice ran in response to whisker stimulation as though they were trying to escape it. By contrast, the ordinary mice ran a little and stopped, even though whisker tweaking continued, like they were able to block out the stimulus. As adults, the fragile X mice ran and changed direction to avoid the whisker stimulator, whereas typical adult mice were able to ignore it.

"Because fragile X syndrome and autism are diseases of abnormal neural development, it's really important to see what is happening at different developmental ages in the animal model," said Cynthia He, the study's first author and a Ph.D. student in Portera-Cailiau's lab.

Researchers also used a special microscope, employing a technique called two-photon calcium imaging, to observe signals from individual brain cells that are activated by stimulation like an object touching whiskers.

An analysis of these observations showed neurons firing equally in both groups of mice in the beginning, then tapering off only in the without fragile X. The researchers hypothesize that the fragile X group may lack chemicals that inhibit neuronal activity, a potential therapeutic target.

"You really need a solid understanding of the physiology in order to develop treatments for neurodevelopmental conditions such as autism," He said. "This is an important step in that direction."

Explore further: Diabetes drug may help symptoms of autism associated condition

More information: Journal of Neuroscience (2017). DOI: 10.1523/JNEUROSCI.0651-17.2017

Related Stories

Diabetes drug may help symptoms of autism associated condition

May 15, 2017
A widely used diabetes medication could help people with a common inherited form of autism, research shows.

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 ...

Treatment window for Fragile X likely doesn't close after childhood

March 20, 2017
Brain samples from humans show that the treatment window for Fragile X syndrome likely remains open well into maturity after childhood, when previous tests with mice indicated it might close, according to a new Drexel University-led ...

New method for the diagnosis of autism found

March 21, 2017
Auditory hypersensitivity is a major complication in autism. Researchers at Mie University in Japan have demonstrated, using a rat autism model, that morphological abnormality of the auditory pathway is involved in this impairment. ...

Study identifies new trigger mechanism for fragile X syndrome in mice

July 5, 2016
A study published today in the Journal of Neuroscience led by Yongjie Yang of Tufts University School of Medicine identifies an astroglial trigger mechanism as contributing to symptoms of fragile X syndrome in mice.

Recommended for you

Epilepsy linked to brain volume and thickness differences

January 22, 2018
Epilepsy is associated with thickness and volume differences in the grey matter of several brain regions, according to new research led by UCL and the Keck School of Medicine of USC.

Research reveals atomic-level changes in ALS-linked protein

January 18, 2018
For the first time, researchers have described atom-by-atom changes in a family of proteins linked to amyotrophic lateral sclerosis (ALS), a group of brain disorders known as frontotemporal dementia and degenerative diseases ...

Fragile X finding shows normal neurons that interact poorly

January 18, 2018
Neurons in mice afflicted with the genetic defect that causes Fragile X syndrome (FXS) appear similar to those in healthy mice, but these neurons fail to interact normally, resulting in the long-known cognitive impairments, ...

How your brain remembers what you had for dinner last night

January 17, 2018
Confirming earlier computational models, researchers at University of California San Diego and UC San Diego School of Medicine, with colleagues in Arizona and Louisiana, report that episodic memories are encoded in the hippocampus ...

Recording a thought's fleeting trip through the brain

January 17, 2018
University of California, Berkeley neuroscientists have tracked the progress of a thought through the brain, showing clearly how the prefrontal cortex at the front of the brain coordinates activity to help us act in response ...

Midbrain 'start neurons' control whether we walk or run

January 17, 2018
Locomotion comprises the most fundamental movements we perform. It is a complex sequence from initiating the first step, to stopping when we reach our goal. At the same time, locomotion is executed at different speeds to ...

0 comments

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.