Testing the stability of neural responses to tactile stimuli in fragile X syndrome mice

Many individuals diagnosed with autism spectrum disorder (ASD) and related neurodevelopmental disorders, like fragile X syndrome (FXS), show alterations in sensory processing. A common example of this phenomenon is heightened sensitivity to auditory or tactile cues. One possibility is that these changes to primary sensory systems are driving the core ASD symptoms in high-level cognitive functions, such as social communication deficits.

To study how sensory processing is altered in ASD, Carlos Portera-Cailliau’s group at the University of California, Los Angeles, has spent several years investigating sensory neural circuits in fragile X mental retardation 1 (Fmr1) knock-out mice, an animal model of fragile X syndrome. Using a range of techniques, Portera-Cailliau’s group has recorded activity in tens to hundreds of cortical neurons from Fmr1 knock-out mice as they are presented with tactile or visual stimuli. Because the data arising from these experiments are large and complex, the Portera-Cailliau group collaborates with Cian O’Donnell’s computational group at the University of Bristol, UK, to help gain extra insights into what is changing in the brains of Fmr1 knock-out mice. Together, they found that the leading excitation/inhibition imbalance theory for ASD and FXS may be too limited to explain the brain circuit alterations underlying these disorders¹.

Now Portera-Cailliau’s and O’Donnell’s teams will ask if neural responses to sensory stimuli in Fmr1 knock-out mice are reliable and stable. To do this, Portera-Cailliau’s team will twitch the whiskers of Fmr1 knock-out mice and record neural responses, then come back to the same mice one week later and repeat the whisker stimulation and obtain recordings from the same neurons. O’Donnell’s group will then apply modern computational analysis methods to the data. If they find that a different set of neurons responded the second time around in the Fmr1 knock-out mice, it could offer a new theory for why sensory signals are problematic for people with fragile X syndrome. In particular, if the sensory parts of the brain respond variably even when the outside world stays the same, this might suggest that other parts of the brain misinterpret these sensory signals and so have difficulty tracking external events in the outside world.