Circuit Dysfunction Underlying Atypical Sensory Processing in Fragile X Syndrome Carlos Portera-Cailliau, M.D., Ph.D. Depts. of Neurology and Neurobiology
David Geffen School of Medicine at UCLA Host: Andres Barria Abstract: 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). For example, using a go/no-go behavior 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-/-micewith a chemogenetic (DREADD) strategy was sufficient to rescue their behavioral performance. Strikingly, human subjects with FXS exhibit similar impairments in visual discrimination as Fmr1-/- mice. These results suggest that manipulating inhibition may help sensory processing in FXS.
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