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  • 标题:Deletion of the mu opioid receptor gene in mice reshapes the reward–aversion connectome
  • 作者:Anna E. Mechling ; Tanzil Arefin ; Hsu-Lei Lee
  • 期刊名称:Proceedings of the National Academy of Sciences
  • 印刷版ISSN:0027-8424
  • 电子版ISSN:1091-6490
  • 出版年度:2016
  • 卷号:113
  • 期号:41
  • 页码:11603-11608
  • DOI:10.1073/pnas.1601640113
  • 语种:English
  • 出版社:The National Academy of Sciences of the United States of America
  • 摘要:Connectome genetics seeks to uncover how genetic factors shape brain functional connectivity; however, the causal impact of a single gene’s activity on whole-brain networks remains unknown. We tested whether the sole targeted deletion of the mu opioid receptor gene (Oprm1) alters the brain connectome in living mice. Hypothesis-free analysis of combined resting-state fMRI diffusion tractography showed pronounced modifications of functional connectivity with only minor changes in structural pathways. Fine-grained resting-state fMRI mapping, graph theory, and intergroup comparison revealed Oprm1-specific hubs and captured a unique Oprm1 gene-to-network signature. Strongest perturbations occurred in connectional patterns of pain/aversion-related nodes, including the mu receptor-enriched habenula node. Our data demonstrate that the main receptor for morphine predominantly shapes the so-called reward/aversion circuitry, with major influence on negative affect centers.
  • 关键词:mouse brain connectivity ; resting-state functional MRI ; diffusion tensor imaging ; mu opioid receptor ; reward/aversion network
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