Date: Wednesday, September 16, 2020
Location: Zoom Webinar – Registration Required
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Speaker: Carlos Portera-Cailliau, M.D., Ph.D.
Affiliation: Professor of Neurology & Neurobiology, David Geffen School of Medicine, University of California, Los Angeles
Host: Dr. Elly Nedivi
Talk title: Interneuron dysfunction in the fragile X mouse model of autism
Abstract: To uncover the circuit-level alterations that underlie atypical sensory processing associated with autism, we have adopted a symptom-to-circuit approach in theFmr1-/- mouse model of Fragile X syndrome (FXS). Using a ‘go/no-go’ visual discrimination 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 in primary visual cortex, and a decrease in the activity of parvalbumin (PV) interneurons. 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 as Fmr1-/- mice. These results suggest that manipulating inhibition may help sensory processing in FXS. More recently, we find that task performance of Fmr1-/- mice is impaired in the presence of visual or auditory distractors, suggesting that sensory hyperarousal may affect perceptual learning in autism, a problem we link to dysfunction of VIP interneurons.