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

Details

• Alternative Title:
  Nat Neurosci
• Personal Author:
  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
• 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.
• Subjects:
  Adolescent Adult Animals Calcium-Calmodulin-Dependent Protein Kinase Type 2 Choice Behavior Discrimination, Psychological Disease Models, Animal Female Fragile X Mental Retardation Protein Fragile X Syndrome Humans Inhibition, Psychological Learning Disabilities Male Mice Mice, Transgenic Neurons Neuropil Oxygen Parvalbumins Perceptual Disorders Receptors, G-Protein-Coupled Visual Cortex Young Adult

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• Keywords:
  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:
  R01 HD054453/HD/NICHD NIH HHSUnited States/ ; U54 HD082008/HD/NICHD NIH HHSUnited States/ ; U01 DD001185/DD/NCBDD CDC HHSUnited States/ ; U01DD001185/ACL/ACL HHSUnited States/ ; K23 MH112936/MH/NIMH NIH HHSUnited States/
• Volume:
  21
• Issue:
  10
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:4b0a58483437a21e40c7ecfb88d5cb7f3fa3cff1ab1fbd70eefe0d61a66dd8f9
• Download URL:
  https://stacks.cdc.gov/view/cdc/59507/cdc_59507_DS1.pdf
• File Type:
  [PDF - 2.18 MB ]