TY - JOUR
T1 - Formation of functional areas in the cerebral cortex is disrupted in a mouse model of autism spectrum disorder
AU - Fenlon, Laura R.
AU - Liu, Sha
AU - Gobius, Ilan
AU - Kurniawan, Nyoman D.
AU - Murphy, Skyle
AU - Moldrich, Randal X.
AU - Richards, Linda J.
N1 - Funding Information:
This research was supported by the National Health and Medical Research Council (NHMRC), Australia project grants 1043045 and 1029975. LRF is supported by an Australian Post-graduate Award. SL was supported by a PhD Scholarship from the Chinese Academy of Sciences with supplemental funding from the Queensland Brain Institute. LJR is supported by a Principal Research Fellowship from the NHMRC. The content of this paper is solely the responsibility of the authors and does not necessarily represent the official views of the NHMRC. We thank the Queensland State Government for supporting the operation of the 16.4 T scanner through the Queensland NMR Network. We thank Ilse Buttiens and Rowan Tweedale for assistance in the preparation of this manuscript.
Publisher Copyright:
© Fenlon et al.
PY - 2015/5/1
Y1 - 2015/5/1
N2 - 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.
AB - 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.
KW - Agenesis of the corpus callosum
KW - Autism spectrum disorders (ASD)
KW - BTBR mice
KW - Cortical area patterning
KW - Diffusion imaging
UR - http://www.scopus.com/inward/record.url?scp=85048081151&partnerID=8YFLogxK
U2 - 10.1186/s13064-015-0033-y
DO - 10.1186/s13064-015-0033-y
M3 - Article
C2 - 25879444
AN - SCOPUS:85048081151
SN - 1749-8104
VL - 10
JO - Neural Development
JF - Neural Development
IS - 1
M1 - 10
ER -