Increased Reliability of Visually-Evoked Activity in Area V1 of the MECP2-Duplication Mouse Model of Autism.
Ryan T AshGanna PalaginaJose A Fernandez-LeonJiyoung ParkRob SeilheimerSangkyun LeeJasdeep SabharwalFredy ReyesJing WangDylan LuMuhammad SarfrazEmmanouil FroudarakisAndreas S ToliasSamuel M WuStelios Manolis SmirnakisPublished in: The Journal of neuroscience : the official journal of the Society for Neuroscience (2022)
Atypical sensory processing is now thought to be a core feature of the autism spectrum. Influential theories have proposed that both increased and decreased neural response reliability within sensory systems could underlie altered sensory processing in autism. Here, we report evidence for abnormally increased reliability of visual-evoked responses in layer 2/3 neurons of adult male and female primary visual cortex in the MECP2-duplication syndrome animal model of autism. Increased response reliability was due in part to decreased response amplitude, decreased fluctuations in endogenous activity, and an abnormal decoupling of visual-evoked activity from endogenous activity. Similar to what was observed neuronally, the optokinetic reflex occurred more reliably at low contrasts in mutant mice compared with controls. Retinal responses did not explain our observations. These data suggest that the circuit mechanisms for combining sensory-evoked and endogenous signal and noise processes may be altered in this form of syndromic autism. SIGNIFICANCE STATEMENT Atypical sensory processing is now thought to be a core feature of the autism spectrum. Influential theories have proposed that both increased and decreased neural response reliability within sensory systems could underlie altered sensory processing in autism. Here, we report evidence for abnormally increased reliability of visual-evoked responses in primary visual cortex of the animal model for MECP2-duplication syndrome, a high-penetrance single-gene cause of autism. Visual-evoked activity was abnormally decoupled from endogenous activity in mutant mice, suggesting in line with the influential "hypo-priors" theory of autism that sensory priors embedded in endogenous activity may have less influence on perception in autism.
Keyphrases
- intellectual disability
- autism spectrum disorder
- mouse model
- machine learning
- adipose tissue
- gene expression
- optical coherence tomography
- deep learning
- type diabetes
- metabolic syndrome
- dna methylation
- diabetic retinopathy
- genome wide
- skeletal muscle
- copy number
- genome wide identification
- optic nerve
- genome wide analysis