TY - JOUR
T1 - Altered structural connectivity networks in a mouse model of complete and partial dysgenesis of the corpus callosum
AU - IRC5 Consortium
AU - Edwards, Timothy J.
AU - Fenlon, Laura R.
AU - Dean, Ryan J.
AU - Bunt, Jens
AU - Sherr, Elliott H.
AU - Richards, Linda J.
N1 - Funding Information:
This work was supported by National Health and Medical Research Council (NHMRC) grants 1126053 and 1124411 and NIH grant NS058721. TJE was supported by a University of Queensland Research Scholarship. LRF was supported by a UQ Development Fellowship and NHMRC Investigator Grant GNT1175825. RJD was supported by Brain Injured Childrens After-Care Recovery Endeavours (BICARE) Inc. LJR was supported by NHMRC Principal Research Fellowship GNT1120615.We thank The University of Queensland Biological Resources and Queensland Brain Institute animal team for animal support and the Queensland Brain Institute Microscopy team for imaging support. We thank Dr. Nyoman Kurniawan for his assistance in acquiring MRI scans at the Centre for Advanced Imaging at The University of Queensland, a National Collaborative Research Infrastructure Strategy funded facility. We thank Prof. Alan Connelly, Dr. Yonghui Li and Dr. Cirong Liu for initial contributions to this project. We thank Prof. Fernanda Tovar-Moll and Dr. Diego Szczupak for input on the manuscript. Finally, we thank the International Research Consortium for the Corpus Callosum and Cerebral Connectivity (IRC5, https://www.irc5.org) researchers for discussions and input. The IRC5 researchers are Glena Andrews, Emanuela Argilli, Filippo Arrigoni, Nadia Bahi-Buisson, Rodrigo Basilio, Anais Bellon, Tania Attie-Bitach, Nathalie Boddaert, Rhonda Booth, Lucille Boutard, Ivanei Bramati, Warren Brown, Jens Bunt, Alain Chedotal, Ryan Dean, Christel Depienne, Jessica Dubois, Timothy Edwards, Laura Fenlon, Catherine Garel, Sonia Garel, Lucas Gemal, Kim Giraudat, Sarah Glatter, Orit Glenn, Juliette Godin, Solveiq Heide, Delphine Heron, Rujii Jiang, Bethany Johnson-Kern, David Kahn, Gregor Kasprian, Dorit Kliemann, Emmanuelle Lacaze, Roberto Lent, Richard Leventer, Marco Leyton, Paul Lockhart, Zoran Lynton, Paul Lockhart, George McGillivray, Theo Marins, Ashley Marsh, Bruno Melo, Cyril Mignot, Anne Elodie Millisher, Ching Moey, Jorge Moll, Myriam Monteiro, Marie-Laur Moutard, Pratik Mukherjee, Remya Nair, Marta Nieto-Lopez, Lynn K Paul, Alessandra Pierrani, Ferechte Encha-Razavi, Linda J Richards, Gail Robinson, Romina Romaniello, Rinuba Rinabuekki,Tally Lerman-Sagie, Laurent Salomon, Elliott H Sherr, Vanessa Siffredi, Myrtille Spentchian, Diego Szcupak, Victor Tarabykin, Sophie Thomas, Fernanda Tovar-Moll, Jasmin Turner, Stephanie Valence, Mark Walterfang, Natalia Rich-Wimmer, Alice Wright, Binnaz Yalcin.
Funding Information:
This work was supported by National Health and Medical Research Council (NHMRC) grants 1126053 and 1124411 and NIH grant NS058721 . TJE was supported by a University of Queensland Research Scholarship. LRF was supported by a UQ Development Fellowship and NHMRC Investigator Grant GNT1175825 . RJD was supported by Brain Injured Childrens After-Care Recovery Endeavours (BICARE) Inc . LJR was supported by NHMRC Principal Research Fellowship GNT1120615 .
Publisher Copyright:
© 2020 The Author(s)
PY - 2020/8/15
Y1 - 2020/8/15
N2 - Corpus callosum dysgenesis (CCD) describes a collection of brain malformations in which the main fiber tract connecting the two hemispheres is either absent (complete CCD, or ‘agenesis of the corpus callosum’) or reduced in size (partial CCD). Humans with these neurodevelopmental disorders have a wide range of cognitive outcomes, including seemingly preserved features of interhemispheric communication in some cases. However, the structural substrates that could underlie this variability in outcome remain to be fully elucidated. Here, for the first time, we characterize the global brain connectivity of a mouse model of complete and partial CCD. We demonstrate features of structural brain connectivity that model those predicted in humans with CCD, including Probst bundles in complete CCD and heterotopic sigmoidal connections in partial CCD. Crucially, we also histologically validate the recently predicted ectopic sigmoid bundle present in humans with partial CCD, validating the utility of this mouse model for fine anatomical studies of this disorder. Taken together, this work describes a mouse model of altered structural connectivity in variable severity CCD and forms a foundation for future studies investigating the function and mechanisms of development of plastic tracts in developmental disorders of brain connectivity.
AB - Corpus callosum dysgenesis (CCD) describes a collection of brain malformations in which the main fiber tract connecting the two hemispheres is either absent (complete CCD, or ‘agenesis of the corpus callosum’) or reduced in size (partial CCD). Humans with these neurodevelopmental disorders have a wide range of cognitive outcomes, including seemingly preserved features of interhemispheric communication in some cases. However, the structural substrates that could underlie this variability in outcome remain to be fully elucidated. Here, for the first time, we characterize the global brain connectivity of a mouse model of complete and partial CCD. We demonstrate features of structural brain connectivity that model those predicted in humans with CCD, including Probst bundles in complete CCD and heterotopic sigmoidal connections in partial CCD. Crucially, we also histologically validate the recently predicted ectopic sigmoid bundle present in humans with partial CCD, validating the utility of this mouse model for fine anatomical studies of this disorder. Taken together, this work describes a mouse model of altered structural connectivity in variable severity CCD and forms a foundation for future studies investigating the function and mechanisms of development of plastic tracts in developmental disorders of brain connectivity.
KW - Brain plasticity
KW - Corpus callosum
KW - Corpus callosum dysgenesis
KW - Cortical development
KW - Neurodevelopmental disorders
KW - Structural connectome
UR - http://www.scopus.com/inward/record.url?scp=85085080696&partnerID=8YFLogxK
U2 - 10.1016/j.neuroimage.2020.116868
DO - 10.1016/j.neuroimage.2020.116868
M3 - Article
C2 - 32360691
AN - SCOPUS:85085080696
VL - 217
JO - NeuroImage
JF - NeuroImage
SN - 1053-8119
M1 - 116868
ER -