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


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.

SUBMITTER: Mechling AE 

PROVIDER: S-EPMC5068324 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature

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

Mechling Anna E AE   Arefin Tanzil T   Lee Hsu-Lei HL   Bienert Thomas T   Reisert Marco M   Ben Hamida Sami S   Darcq Emmanuel E   Ehrlich Aliza A   Gaveriaux-Ruff Claire C   Parent Maxime J MJ   Rosa-Neto Pedro P   Hennig Jürgen J   von Elverfeldt Dominik D   Kieffer Brigitte Lina BL   Harsan Laura-Adela LA  

Proceedings of the National Academy of Sciences of the United States of America 20160926 41


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 pathwa  ...[more]

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