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

Proc Natl Acad Sci U S A. 2016 Oct 11;113(41):11603-11608. doi: 10.1073/pnas.1601640113. Epub 2016 Sep 26.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / physiology*
  • Brain Mapping / methods
  • Connectome* / methods
  • Diffusion Tensor Imaging
  • Gene Deletion*
  • Genotype
  • Magnetic Resonance Imaging
  • Male
  • Mice
  • Models, Neurological
  • Receptors, Opioid, mu / genetics*
  • Receptors, Opioid, mu / metabolism
  • Reward*


  • Receptors, Opioid, mu