Published October 2018 | Nature Neuroscience

Fragile X syndrome manifests itself in many ways, including developmental delays, mild to moderate intellectual disability, ADHD symptoms, autism spectrum disorder, and seizure disorders.

In fragile X syndrome, impairment of visual discrimination is a common symptom. This is the ability to recognize details in visual images, such as the direction objects are moving. In a unique translational collaboration between Cincinnati Children’s and UCLA, researchers isolated the cognitive problem in mice and in humans with fragile X and reversed the problem in mice.

Many clinical trials in people who have fragile X have failed to duplicate promising results found in mouse models. “One reason for that is the task you give mice is not equivalent to the human task. Like T-mazes and rotarods—those aren’t tasks you can do in humans,” says Lauren Schmitt, PhD. “We’re trying to push the field forward, building translational models where we can do the exact same kind of thing in the mouse and the human.”

To address this problem, UCLA bench scientists and Cincinnati Children’s clinical researchers developed two go/no-go tasks for mice and humans. “This was one of the first studies of its kind where researchers developed a human model task alongside bench scientists as they developed an equivalent mouse model task,” says Schmitt.

In each task, mice and humans had to recognize the directional orientation of moving objects. In both cases, fragile X mice and humans failed. In the mice, neuroscientists took the research a step further and found that the perceptual impairment was associated with reduced activity in parvalbumin interneurons in the primary visual cortex. When researchers restored activity in these neurons, the associated cognitive skill was recovered, too.

“This gives families hope that if you’re able to rescue a deficit in mice, then perhaps later down the road, we can also rescue this deficit in individuals with fragile X,” Schmitt says.