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Proc Natl Acad Sci U S A. 2016 Oct 11;113(41):11603-11608. Epub 2016 Sep 26.

Deletion of the mu opioid receptor gene in mice reshapes the reward-aversion connectome.

Author information

1
Advanced Molecular Imaging Center, Medical Physics, University Medical Center Freiburg, 79106 Freiburg, Germany; Faculty of Biology, University of Freiburg, 79104 Freiburg, Germany.
2
Advanced Molecular Imaging Center, Medical Physics, University Medical Center Freiburg, 79106 Freiburg, Germany; Bernstein Center for Computational Neuroscience, University of Freiburg, 79104 Freiburg, Germany.
3
Advanced Molecular Imaging Center, Medical Physics, University Medical Center Freiburg, 79106 Freiburg, Germany.
4
Department of Translational Medicine and Neurogenetics, Institut de Génétique et de Biologie Moléculaire et Cellulaire, Illkirch-Graffenstaden 67400, France; Department of Psychiatry, Douglas Hospital Research Center, School of Medicine, McGill University, Montreal, QC, Canada H3A 1A1.
5
Department of Psychiatry, Douglas Hospital Research Center, School of Medicine, McGill University, Montreal, QC, Canada H3A 1A1.
6
Department of Translational Medicine and Neurogenetics, Institut de Génétique et de Biologie Moléculaire et Cellulaire, Illkirch-Graffenstaden 67400, France.
7
Translational Neuroimaging Laboratory, Douglas Hospital Research Center, McGill University, Montreal, QC, Canada H3A 1A1.
8
Department of Translational Medicine and Neurogenetics, Institut de Génétique et de Biologie Moléculaire et Cellulaire, Illkirch-Graffenstaden 67400, France; Department of Psychiatry, Douglas Hospital Research Center, School of Medicine, McGill University, Montreal, QC, Canada H3A 1A1; harsan@unistra.fr Brigitte.Kieffer@douglas.mcgill.ca.
9
Advanced Molecular Imaging Center, Medical Physics, University Medical Center Freiburg, 79106 Freiburg, Germany; Engineering Science, Computer Science, and Imaging Laboratory, Integrative Multimodal Imaging in Healthcare, UMR 7357, University of Strasbourg, CNRS, 67000 Strasbourg, France; Department of Biophysics and Nuclear Medicine, University Hospital Strasbourg, 67000 Strasbourg, France harsan@unistra.fr Brigitte.Kieffer@douglas.mcgill.ca.

Abstract

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.

KEYWORDS:

diffusion tensor imaging; mouse brain connectivity; mu opioid receptor; resting-state functional MRI; reward/aversion network

PMID:
27671662
PMCID:
PMC5068324
DOI:
10.1073/pnas.1601640113
[Indexed for MEDLINE]
Free PMC Article

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