Scientific article
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English

A common computational and neural anomaly across mouse models of autism

Published inNature neuroscience, vol. 28, no. 7, p. 1519-1532
Publication date2025-07
First online date2025-06-03
Abstract

Computational psychiatry studies suggest that individuals with autism spectrum disorder (ASD) inflexibly update their expectations. Here we leveraged high-yield rodent psychophysics, extensive behavioral modeling and brain-wide single-cell extracellular recordings to assess whether mice with different genetic perturbations associated with ASD show this same computational anomaly, and if so, what neurophysiological features are shared across genotypes. Mice harboring mutations in Fmr1, Cntnap2 or Shank3B show a blunted update of priors during decision-making. Compared with mice that flexibly updated their priors, inflexible updating of priors was associated with a shift in the weighting of prior encoding from sensory to frontal cortices. Furthermore, frontal areas in mouse models of ASD showed more units encoding deviations from the animals' long-run prior, and sensory responses did not differentiate between expected and unexpected observations. These findings suggest that distinct genetic instantiations of ASD may yield common neurophysiological and behavioral phenotypes.

Keywords
  • Animals
  • Autism Spectrum Disorder / genetics
  • Autism Spectrum Disorder / physiopathology
  • Autistic Disorder / genetics
  • Autistic Disorder / physiopathology
  • Brain / physiopathology
  • Disease Models, Animal
  • Fragile X Mental Retardation Protein / genetics
  • Male
  • Membrane Proteins / genetics
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Microfilament Proteins
  • Nerve Tissue Proteins / genetics
  • Neurons / physiology
Funding
  • U.S. Department of Health & Human Services | National Institutes of Health (NIH) [K99NS128075]
  • Wellcome Trust [216324]
  • NINDS NIH HHS [R00 NS128075]
  • NCATS NIH HHS [UM1 TR004405]
Citation (ISO format)
NOEL, Jean-Paul et al. A common computational and neural anomaly across mouse models of autism. In: Nature neuroscience, 2025, vol. 28, n° 7, p. 1519–1532. doi: 10.1038/s41593-025-01965-8
Main files (2)
Article (Published version)
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Article (Accepted version)
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Identifiers
Additional URL for this publicationhttps://www.nature.com/articles/s41593-025-01965-8
Journal ISSN1097-6256
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