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

TitleDeletion of the mu opioid receptor gene in mice reshapes the reward-aversion connectome.
Publication TypeJournal Article
Year of Publication2016
AuthorsMechling AE, Arefin T, Lee H-L, Bienert T, Reisert M, Ben Hamida S, Darcq E, Ehrlich A, Gaveriaux-Ruff C, Parent MJ, Rosa-Neto P, Hennig J, von Elverfeldt D, Kieffer BL, Harsan L-A
JournalProc Natl Acad Sci U S A
Date Published2016 Oct 11

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.

Alternate JournalProc. Natl. Acad. Sci. U.S.A.
PubMed ID27671662
PubMed Central IDPMC5068324