Details:

Alternative Title:
Nat Neurosci
Personal Author:
Goel, Anubhuti ; Cantu, Daniel A. ; Guilfoyle, Janna ; Chaudhari, Gunvant R. ; Newadkar, Aditi ; ... More +
Goel, Anubhuti ; Cantu, Daniel A. ; Guilfoyle, Janna ; Chaudhari, Gunvant R. ; Newadkar, Aditi ; Todisco, Barbara ; de Alba, Diego ; Kourdougli, Nazim ; Schmitt, Lauren M. ; Pedapati, Ernest ; Erickson, Craig A. ; Portera-Cailliau, Carlos Less -
Description:
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.
Subject:
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Article
Autism Spectrum Disorders
DREADD
Fmr1 Knockout, Inhibition
Layer 2/3
Visual Cortex

Source:
Nat Neurosci. 21(10):1404-1411
Pubmed ID:
30250263
Pubmed Central ID:
PMC6161491
Document Type:
Journal Article
Funding:
K23 MH112936/MH/NIMH NIH HHS/United States ; R01 HD054453/HD/NICHD NIH HHS/United States ; U01 DD001185/DD/NCBDD CDC HHS/United States ; U54 HD082008/HD/NICHD NIH HHS/United States
K23 MH112936/MH/NIMH NIH HHS/United States ; R01 HD054453/HD/NICHD NIH HHS/United States ; U01 DD001185/DD/NCBDD CDC HHS/United States ; U54 HD082008/HD/NICHD NIH HHS/United States Less -
Collection(s):
CDC Public Access
Main Document Checksum:
[+]
urn:sha256:4b0a58483437a21e40c7ecfb88d5cb7f3fa3cff1ab1fbd70eefe0d61a66dd8f9
File Type:

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