Description:

The department of Physiology welcomes Carlos Portera-Cailliau, M.D., Ph.D.

To uncover the circuit-level alterations that underlie atypical sensory processing associated with autism, we have adopted a symptom-to-circuit approach in the Fmr1-/- mouse model of Fragile X syndrome (FXS). Using a go/no-go task and in vivo 2-photon calcium imaging, we find that impaired visual discrimination in Fmr1-/- mice correlates with marked deficits in orientation tuning of principal neurons, and a decrease in the activity of parvalbumin (PV) interneurons in primary visual cortex. Restoring visually evoked activity in PV cells in Fmr1-/-mice with a chemogenetic (DREADD) strategy was sufficient to rescue their behavioral performance. Strikingly, human subjects with FXS exhibit similar impairments in visual discrimination asFmr1-/- mice. These results suggest that manipulating inhibition may help sensory processing in FXS. More recently, we find that the ability of Fmr1-/- mice to perform the visual discrimination task is also drastically impaired in the presence of visual or auditory distractors, suggesting that sensory hypersensitivity may affect higher order perceptual learning in autism.”