title: A mu-delta opioid receptor brain atlas reveals neuronal co-occurrence in subcortical networks.
abstract: Opioid receptors are G protein-coupled receptors (GPCRs) that modulate brain function at all levels of neural integration, including autonomic, sensory, emotional and cognitive processing. Mu (MOR) and delta (DOR) opioid receptors functionally interact in vivo, but whether interactions occur at circuitry, cellular or molecular levels remains unsolved. To challenge the hypothesis of MOR/DOR heteromerization in the brain, we generated redMOR/greenDOR double knock-in mice and report dual receptor mapping throughout the nervous system. Data are organized as an interactive database offering an opioid receptor atlas with concomitant MOR/DOR visualization at subcellular resolution, accessible online. We also provide co-immunoprecipitation-based evidence for receptor heteromerization in these mice. In the forebrain, MOR and DOR are mainly detected in separate neurons, suggesting system-level interactions in high-order processing. In contrast, neuronal co-localization is detected in subcortical networks essential for survival involved in eating and sexual behaviors or perception and response to aversive stimuli. In addition, potential MOR/DOR intracellular interactions within the nociceptive pathway offer novel therapeutic perspectives.
authors.affiliation: Department of Neurogenetics and Translational Medicine, Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS, INSERM, Université de Strasbourg, 1 rue Laurent Fries, BP10142, 67404, Illkirch cedex, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Erbs
authors.forename: Lauren
authors.initials: L
authors.lastname: Faget
authors.forename: Gregory
authors.initials: G
authors.lastname: Scherrer
authors.forename: Audrey
authors.initials: A
authors.lastname: Matifas
authors.forename: Dominique
authors.initials: D
authors.lastname: Filliol
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Vonesch
authors.forename: Marc
authors.initials: M
authors.lastname: Koch
authors.forename: Pascal
authors.initials: P
authors.lastname: Kessler
authors.forename: Didier
authors.initials: D
authors.lastname: Hentsch
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Birling
authors.forename: Manoussos
authors.initials: M
authors.lastname: Koutsourakis
authors.forename: Laurent
authors.initials: L
authors.lastname: Vasseur
authors.forename: Pierre
authors.initials: P
authors.lastname: Veinante
authors.forename: Brigitte L
authors.initials: BL
authors.lastname: Kieffer
authors.forename: Dominique
authors.initials: D
authors.lastname: Massotte
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism*; D005260:Female; D055879:Gene Knock-In Techniques; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009415:Nerve Net / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D017465:Receptors, Opioid, delta / Q000032:analysis*; D017450:Receptors, Opioid, mu / Q000032:analysis*
chemical_list: D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu