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Formation of functional areas in the cerebral cortex is disrupted in a mouse model of autism spectrum disorder
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 id...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4412039/ https://www.ncbi.nlm.nih.gov/pubmed/25879444 http://dx.doi.org/10.1186/s13064-015-0033-y |
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author | Fenlon, Laura R Liu, Sha Gobius, Ilan Kurniawan, Nyoman D Murphy, Skyle Moldrich, Randal X Richards, Linda J |
author_facet | Fenlon, Laura R Liu, Sha Gobius, Ilan Kurniawan, Nyoman D Murphy, Skyle Moldrich, Randal X Richards, Linda J |
author_sort | Fenlon, Laura R |
collection | PubMed |
description | 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13064-015-0033-y) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-4412039 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-44120392015-04-29 Formation of functional areas in the cerebral cortex is disrupted in a mouse model of autism spectrum disorder Fenlon, Laura R Liu, Sha Gobius, Ilan Kurniawan, Nyoman D Murphy, Skyle Moldrich, Randal X Richards, Linda J Neural Dev Research Article 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13064-015-0033-y) contains supplementary material, which is available to authorized users. BioMed Central 2015-04-03 /pmc/articles/PMC4412039/ /pubmed/25879444 http://dx.doi.org/10.1186/s13064-015-0033-y Text en © Fenlon et al.; licensee BioMed Central. 2015 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Article Fenlon, Laura R Liu, Sha Gobius, Ilan Kurniawan, Nyoman D Murphy, Skyle Moldrich, Randal X Richards, Linda J Formation of functional areas in the cerebral cortex is disrupted in a mouse model of autism spectrum disorder |
title | Formation of functional areas in the cerebral cortex is disrupted in a mouse model of autism spectrum disorder |
title_full | Formation of functional areas in the cerebral cortex is disrupted in a mouse model of autism spectrum disorder |
title_fullStr | Formation of functional areas in the cerebral cortex is disrupted in a mouse model of autism spectrum disorder |
title_full_unstemmed | Formation of functional areas in the cerebral cortex is disrupted in a mouse model of autism spectrum disorder |
title_short | Formation of functional areas in the cerebral cortex is disrupted in a mouse model of autism spectrum disorder |
title_sort | formation of functional areas in the cerebral cortex is disrupted in a mouse model of autism spectrum disorder |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4412039/ https://www.ncbi.nlm.nih.gov/pubmed/25879444 http://dx.doi.org/10.1186/s13064-015-0033-y |
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