Deletion of the mu opioid receptor gene in mice reshapes the reward-aversion connectome.
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.
Advanced Molecular Imaging Center, Medical Physics, University Medical Center Freiburg, 79106 Freiburg, Germany; Faculty of Biology, University of Freiburg, 79104 Freiburg, Germany.
Anna E
AE
Mechling
Advanced Molecular Imaging Center, Medical Physics, University Medical Center Freiburg, 79106 Freiburg, Germany; Bernstein Center for Computational Neuroscience, University of Freiburg, 79104 Freiburg, Germany.
Tanzil
T
Arefin
Advanced Molecular Imaging Center, Medical Physics, University Medical Center Freiburg, 79106 Freiburg, Germany.
Hsu-Lei
HL
Lee
Advanced Molecular Imaging Center, Medical Physics, University Medical Center Freiburg, 79106 Freiburg, Germany.
Thomas
0000-0002-3775-8320
T
Bienert
Advanced Molecular Imaging Center, Medical Physics, University Medical Center Freiburg, 79106 Freiburg, Germany.
Marco
M
Reisert
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.
Sami
S
Ben Hamida
Department of Psychiatry, Douglas Hospital Research Center, School of Medicine, McGill University, Montreal, QC, Canada H3A 1A1.
Emmanuel
E
Darcq
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.
Aliza
A
Ehrlich
Department of Translational Medicine and Neurogenetics, Institut de Génétique et de Biologie Moléculaire et Cellulaire, Illkirch-Graffenstaden 67400, France.
Claire
C
Gaveriaux-Ruff
Translational Neuroimaging Laboratory, Douglas Hospital Research Center, McGill University, Montreal, QC, Canada H3A 1A1.
Maxime J
MJ
Parent
Translational Neuroimaging Laboratory, Douglas Hospital Research Center, McGill University, Montreal, QC, Canada H3A 1A1.
Pedro
P
Rosa-Neto
Advanced Molecular Imaging Center, Medical Physics, University Medical Center Freiburg, 79106 Freiburg, Germany.
Jürgen
J
Hennig
Advanced Molecular Imaging Center, Medical Physics, University Medical Center Freiburg, 79106 Freiburg, Germany.
Dominik
D
von Elverfeldt
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.
Brigitte Lina
BL
Kieffer
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.
Laura-Adela
LA
Harsan
D000818:Animals; D001921:Brain / Q000502:physiology*; D001931:Brain Mapping / Q000379:methods; D063132:Connectome / Q000379:methods; D056324:Diffusion Tensor Imaging; D017353:Gene Deletion; D005838:Genotype; D008279:Magnetic Resonance Imaging; D008297:Male; D051379:Mice; D008959:Models, Neurological; D017450:Receptors, Opioid, mu / Q000235:genetics* / Q000378:metabolism; D012201:Reward
D017450:Receptors, Opioid, mu
diffusion tensor imaging; mouse brain connectivity; mu opioid receptor; resting-state functional MRI; reward/aversion network
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