A mu-delta opioid receptor brain atlas reveals neuronal co-occurrence in subcortical networks.
A mu-delta opioid receptor brain atlas reveals neuronal co-occurrence in subcortical networks.
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DOI：
10.1007/s00429-014-0717-9
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发表时间：
2015-03
影响因子：
3.1
通讯作者：
Massotte D
中科院分区：
文献类型：
--
作者：
Erbs E;Faget L;Scherrer G;Matifas A;Filliol D;Vonesch JL;Koch M;Kessler P;Hentsch D;Birling MC;Koutsourakis M;Vasseur L;Veinante P;Kieffer BL;Massotte D
阿片受体是G蛋白偶联受体（gpcr），在神经整合的各个层面调节大脑功能，包括自主神经、感觉、情绪和认知处理。Mu （MOR）和delta （DOR）阿片受体在体内功能相互作用，但相互作用是否发生在电路，细胞或分子水平仍未解决。为了挑战大脑中MOR/DOR异质化的假设，我们产生了redMOR/greenDOR双敲入小鼠，并报告了整个神经系统的双受体定位。数据被组织成一个交互式数据库，提供阿片受体图谱，并伴有亚细胞分辨率的MOR/DOR可视化，可在线访问。我们还为这些小鼠的受体异聚化提供了基于免疫共沉淀的证据。在前脑中，MOR和DOR主要在单独的神经元中检测到，表明在高阶加工中存在系统级相互作用。相比之下，神经元共定位在皮层下网络中被检测到，这些网络对生存至关重要，涉及饮食和性行为或对厌恶刺激的感知和反应。此外，在伤害性通路中潜在的MOR/DOR细胞内相互作用提供了新的治疗前景。本文的在线版本（doi:10.1007/s00429-014-0717-9）包含补充材料，仅供授权用户使用。
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. The online version of this article (doi:10.1007/s00429-014-0717-9) contains supplementary material, which is available to authorized users.