title: Altered structural connectome in adolescent socially isolated mice.
abstract: Social experience is essential for adolescent development and plasticity of social animals. Deprivation of the experience by social isolation impairs white matter microstructures in the prefrontal cortex. However, the effect of social isolation may involve highly distributed brain networks, and therefore cannot be fully explained by a change of a single region. Here, we compared the connectomes of adolescent socially-isolated mice and normal-housed controls via diffusion magnetic resonance imaging. The isolated mice displayed an abnormal connectome, characterized by an increase in degree and reductions in measures such as modularity, small-worldness, and betweenness. The increase in degree was most evident in the dorsolateral orbitofrontal cortex, entorhinal cortex, and perirhinal cortex. In a connection-wise comparison, we revealed that most of the abnormal edges were inter-modular and inter-hemispheric connections of the dorsolateral orbitofrontal cortex. Further tractography-based analyses and histological examinations revealed microstructural changes in the forceps minor and lateral-cortical tracts that were associated with the dorsolateral orbitofrontal cortex. These changes of connectomes were correlated with fear memory deficits and hyper-locomotion activities induced by social isolation. Considering the key role of the orbitofrontal cortex in social behaviors, adolescent social isolation may primarily disrupt the orbitofrontal cortex and its neural pathways thereby contributing to an abnormal structural connectome.
authors.affiliation: Queensland Brain Institute, The University of Queensland, Brisbane, QLD 4072, Australia; Brainnetome Center, Institute of Automation, Chinese Academy of Sciences, Beijing 100190, China; National Laboratory of Pattern Recognition, Institute of Automation, Chinese Academy of Sciences, Beijing 100190, China.
authors.forename: Cirong
authors.initials: C
authors.lastname: Liu
authors.affiliation: Queensland Brain Institute, The University of Queensland, Brisbane, QLD 4072, Australia.
authors.forename: Yonghui
authors.initials: Y
authors.lastname: Li
authors.affiliation: Queensland Brain Institute, The University of Queensland, Brisbane, QLD 4072, Australia.
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Edwards
authors.affiliation: The Centre for Advanced Imaging, The University of Queensland, Brisbane, QLD 4072, Australia.
authors.forename: Nyoman D
authors.initials: ND
authors.lastname: Kurniawan
authors.affiliation: Queensland Brain Institute, The University of Queensland, Brisbane, QLD 4072, Australia; The School of Biomedical Sciences, The University of Queensland, Brisbane, QLD 4072, Australia.
authors.forename: Linda J
authors.initials: LJ
authors.lastname: Richards
authors.affiliation: Queensland Brain Institute, The University of Queensland, Brisbane, QLD 4072, Australia; Brainnetome Center, Institute of Automation, Chinese Academy of Sciences, Beijing 100190, China; National Laboratory of Pattern Recognition, Institute of Automation, Chinese Academy of Sciences, Beijing 100190, China; Key Laboratory for NeuroInformation of Ministry of Education, School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu 610054, China. Electronic address: jiangtz@nlpr.ia.ac.cn.
authors.forename: Tianzi
authors.initials: T
authors.lastname: Jiang
mesh_terms: D000818:Animals; D001921:Brain / Q000473:pathology*; D003214:Conditioning, Classical; D063132:Connectome; D038524:Diffusion Magnetic Resonance Imaging; D005239:Fear; D005260:Female; D008297:Male; D008570:Memory, Short-Term; D008810:Mice, Inbred C57BL; D009043:Motor Activity; D009434:Neural Pathways / Q000473:pathology; D012934:Social Isolation
keywords: Brain network; Connectome; Diffusion MRI; Orbitofrontal cortex; Social deprivation; Structural connectivity