Journal Article

Impaired perceptual learning in a mouse model of Fragile X syndrome is mediated by parvalbumin neuron dysfunction and is reversible

Newadkar, Aditi, Portera-Cailliau, Carlos, Goel, Anubhuti, Cantu, Daniel A, Chaudhari, Gunvant R, Kourdougli, Nazim, Erickson, Craig A, Guilfoyle, Janna, Todisco, Barbara, Schmitt, Lauren M, Pedapati, Ernest, de Alba, Diego

2018

Overview

To uncover the circuit-level alterations that underlie atypical sensory processing associated with autism, we adopted a symptom-to-circuit approach in the Fmr1-knockout (Fmr1–/–) mouse model of Fragile X syndrome. Using a go/no-go task and in vivo two-photon calcium imaging, we find that impaired visual discrimination in Fmr1–/– mice correlates with marked deficits in orientation tuning of principal neurons and with a decrease in the activity of parvalbumin interneurons in primary visual cortex. Restoring visually evoked activity in parvalbumin cells in Fmr1–/– mice with a chemogenetic strategy using designer receptors exclusively activated by designer drugs was sufficient to rescue their behavioral performance. Strikingly, human subjects with Fragile X syndrome exhibit impairments in visual discrimination similar to those in Fmr1–/– mice. These results suggest that manipulating inhibition may help sensory processing in Fragile X syndrome.

• Publisher: Nature Publishing Group
• Subject: Autism / Calcium / Calcium imaging / Circuits / FMR1 protein / Fragile X syndrome / Go/no-go discrimination learning / Human behavior / Human performance / Information processing / Intellectual disabilities / Interneurons / Mice / Neuroimaging / Orientation behavior / Parvalbumin / Photovoltaic cells / Receptors / Sensory integration / Sensory perception / Somatosensory cortex / Visual cortex / Visual discrimination