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. and Richards, Linda J. (2015) Formation of functional areas in the cerebral cortex is disrupted in a mouse model of autism spectrum disorder. Neural Development, 10 10: 1-14. doi:10.1186/s13064-015-0033-y


Author Fenlon, Laura R.
Liu, Sha
Gobius, Ilan
Kurniawan, Nyoman D.
Murphy, Skyle
Moldrich, Randal X.
Richards, Linda J.
Title Formation of functional areas in the cerebral cortex is disrupted in a mouse model of autism spectrum disorder
Journal name Neural Development   Check publisher's open access policy
ISSN 1749-8104
Publication date 2015-05-01
Year available 2015
Sub-type Article (original research)
DOI 10.1186/s13064-015-0033-y
Open Access Status DOI
Volume 10
Issue 10
Start page 1
End page 14
Total pages 14
Place of publication London United Kingdom
Publisher BioMed Central
Collection year 2016
Language eng
Formatted 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.
Keyword Agenesis of the corpus callosum
Autism spectrum disorders (ASD)
BTBR mice
Cortical area patterning
Diffusion imaging
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

 
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