title: Formation of functional areas in the cerebral cortex is disrupted in a mouse model of autism spectrum disorder.
abstract: BACKGROUND
  Autism spectrum disorders (ASD) are a group of poorly understood behavioural disorders, which have increased in prevalence in the past two decades. Animal models offer the opportunity to understand the biological basis of these disorders. Studies comparing different mouse strains have identified the inbred BTBR T + tf/J (BTBR) strain as a mouse model of ASD based on its anti-social and repetitive behaviours. Adult BTBR mice have complete agenesis of the corpus callosum, reduced cortical thickness and changes in early neurogenesis. However, little is known about the development or ultimate organisation of cortical areas devoted to specific sensory and motor functions in these mice that may also contribute to their behavioural phenotype.
  
  
  RESULTS
  In this study, we performed diffusion tensor imaging and tractography, together with histological analyses to investigate the emergence of functional areas in the cerebral cortex and their connections in BTBR mice and age-matched C57Bl/6 control mice. We found evidence that neither the anterior commissure nor the hippocampal commissure compensate for the loss of callosal connections, indicating that no interhemispheric neocortical connectivity is present in BTBR mice. We also found that both the primary visual and somatosensory cortical areas are shifted medially in BTBR mice compared to controls and that cortical thickness is differentially altered in BTBR mice between cortical areas and throughout development.
  
  
  CONCLUSIONS
  We demonstrate that interhemispheric connectivity and cortical area formation are altered in an age- and region-specific manner in BTBR mice, which may contribute to the behavioural deficits previously observed in this strain. Some of these developmental patterns of change are also present in human ASD patients, and elucidating the aetiology driving cortical changes in BTBR mice may therefore help to increase our understanding of this disorder.
authors: Queensland Brain Institute, The University of Queensland, Building 79, St Lucia Campus, Brisbane, QLD, 4072, Australia. l.fenlon@uq.edu.au.
authors: Laura R
authors: LR
authors: Fenlon
authors: Queensland Brain Institute, The University of Queensland, Building 79, St Lucia Campus, Brisbane, QLD, 4072, Australia. sha.liu@uqconnect.edu.au.
authors: Sha
authors: S
authors: Liu
authors: Queensland Brain Institute, The University of Queensland, Building 79, St Lucia Campus, Brisbane, QLD, 4072, Australia. i.gobius@uq.edu.au.
authors: Ilan
authors: I
authors: Gobius
authors: Centre for Advanced Imaging, The University of Queensland, Brisbane, QLD, 4072, Australia. nyoman.kurniawan@cai.uq.edu.au.
authors: Nyoman D
authors: ND
authors: Kurniawan
authors: Queensland Brain Institute, The University of Queensland, Building 79, St Lucia Campus, Brisbane, QLD, 4072, Australia. skyle.murphy@griffithuni.edu.au.
authors: Skyle
authors: S
authors: Murphy
authors: Queensland Brain Institute, The University of Queensland, Building 79, St Lucia Campus, Brisbane, QLD, 4072, Australia. r.moldrich@uq.edu.au.|Current address: UQ Centre for Clinical Research, The University of Queensland, Royal Brisbane & Women's Hospital Campus, Brisbane, Queensland, 4029, Australia. r.moldrich@uq.edu.au.
authors: Randal X
authors: RX
authors: Moldrich
authors: Queensland Brain Institute, The University of Queensland, Building 79, St Lucia Campus, Brisbane, QLD, 4072, Australia. richards@uq.edu.au.|The School of Biomedical Sciences, The University of Queensland, St Lucia Campus, Brisbane, QLD, 4072, Australia. richards@uq.edu.au.
authors: Linda J
authors: LJ
authors: Richards
mesh_terms: D061085:Agenesis of Corpus Callosum / Q000235:genetics / Q000473:pathology; D000375:Aging / Q000473:pathology; D000818:Animals; D066240:Anterior Commissure, Brain / Q000473:pathology; D000067877:Autism Spectrum Disorder / Q000473:pathology*; D002540:Cerebral Cortex / Q000473:pathology*; D056324:Diffusion Tensor Imaging; D004195:Disease Models, Animal; D020712:Fornix, Brain / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D008818:Mice, Neurologic Mutants; D010641:Phenotype; D013003:Somatosensory Cortex / Q000473:pathology; D014793:Visual Cortex / Q000473:pathology