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Nat Neurosci. 2018 Oct;21(10):1404-1411. doi: 10.1038/s41593-018-0231-0. Epub 2018 Sep 24.

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

Author information

1
Department of Neurology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
2
Department of Psychiatry, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
3
Department of Neurology, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
4
Department of Neurology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA. cpcailliau@mednet.ucla.edu.
5
Department of Neurobiology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA. cpcailliau@mednet.ucla.edu.

Abstract

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.

PMID:
30250263
PMCID:
PMC6161491
DOI:
10.1038/s41593-018-0231-0
[Indexed for MEDLINE]
Free PMC Article

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