title: Disruption of visual circuit formation and refinement in a mouse model of autism.
abstract: Aberrant connectivity is believed to contribute to the pathophysiology of autism spectrum disorder (ASD). Recent neuroimaging studies have increasingly identified such impairments in patients with ASD, including alterations in sensory systems. However, the cellular substrates and molecular underpinnings of disrupted connectivity remain poorly understood. Utilizing eye-specific segregation in the dorsal lateral geniculate nucleus (dLGN) as a model system, we investigated the formation and refinement of precise patterning of synaptic connections in the BTBR T + tf/J (BTBR) mouse model of ASD. We found that at the neonatal stage, the shape of the dLGN occupied by retinal afferents was altered in the BTBR group compared to C57BL/6J (B6) animals. Notably, the degree of overlap between the ipsi- and contralateral afferents was significantly greater in the BTBR mice. Moreover, these abnormalities continued into mature stage in the BTBR animals, suggesting persistent deficits rather than delayed maturation of axonal refinement. Together, these results indicate disrupted connectivity at the synaptic patterning level in the BTBR mice, suggesting that in general, altered neural circuitry may contribute to autistic behaviours seen in this animal model. In addition, these data are consistent with the notion that lower-level, primary processing mechanisms contribute to altered visual perception in ASD. Autism Res 2017, 10: 212-223. © 2016 The Authors Autism Research published by Wiley Periodicals, Inc. on behalf of International Society for Autism Research.
authors.affiliation: Developmental Neurosciences Research Program, Alberta Children's Hospital Research Institute (ACHRI), Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Ning
authors.identifier: http://orcid.org/0000-0003-0300-9791
authors.initials: N
authors.lastname: Cheng
authors.affiliation: Developmental Neurosciences Research Program, Alberta Children's Hospital Research Institute (ACHRI), Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Maryam
authors.initials: M
authors.lastname: Khanbabaei
authors.affiliation: Department of Electrical and Computer Engineering, Schulich School of Engineering, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Kartikeya
authors.initials: K
authors.lastname: Murari
authors.affiliation: Departments of Pediatrics, Clinical Neurosciences, Physiology & Pharmacology, Alberta Children's Hospital Research Institute and Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Jong M
authors.initials: JM
authors.lastname: Rho
mesh_terms: D000818:Animals; D000067877:Autism Spectrum Disorder / Q000503:physiopathology*; D004195:Disease Models, Animal; D005829:Geniculate Bodies / Q000503:physiopathology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D018613:Microscopy, Confocal / Q000379:methods; D065866:Optic Tract / Q000503:physiopathology*
keywords: BTBR mouse; autism spectrum disorder; brain circuit; eye-specific segregation; lateral geniculate nucleus; synaptic patterning; visual system