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Parallel ascending spinal pathways for affective touch and pain

机译：平行上升的脊柱，用于情感触摸和疼痛

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摘要

The anterolateral pathway consists of ascending spinal tracts that convey pain, temperature and touch information from the spinal cord to the brain~(1-4). Projection neurons of the anterolateral pathway are attractive therapeutic targets for pain treatment because nociceptive signals emanating from the periphery are channelled through these spinal projection neurons en route to the brain. However, the organizational logic of the anterolateral pathway remains poorly understood. Here we show that two populations of projection neurons that express the structurally related G-protein-coupled receptors (GPCRs) TACR1 and GPR83 form parallel ascending circuit modules that cooperate to convey thermal, tactile and noxious cutaneous signals from the spinal cord to the lateral parabrachial nucleus of the pons. Within this nucleus, axons of spinoparabrachial (SPB) neurons that express Tacr1 or Gpr83 innervate distinct sets of subnuclei, and strong optogenetic stimulation of the axon terminals induces distinct escape behaviours and autonomic responses. Moreover, SPB neurons that  express Gpr83 are highly sensitive to cutaneous mechanical stimuli and receive strong synaptic inputs from both high- and low-threshold primary mechanosensory neurons. Notably, the valence associated with activation of SPB neurons that express Gpr83 can be either positive or negative, depending on stimulus intensity. These findings reveal anatomically, physiologically and functionally distinct subdivisions of the SPB tract that underlie affective aspects of touch and pain.
机译：前外途径由升高的脊柱组成，从脊髓到大脑的疼痛，温度和触摸信息传达疼痛，温度和触摸信息〜（1-4）。前外途径的投影神经元是疼痛治疗的有吸引力的治疗靶标，因为从周边发出的伤害性信号通过这些脊柱投影神经元通向大脑。然而，前外侧途径的组织逻辑仍然清晰。在这里，我们表明，两种投影神经元的群体表达结构相关的G蛋白偶联受体（GPRS）TACR1和GPR83形成并行上升电路模块，该模块配合从脊髓到横向曲线的热，触觉和有害的皮肤信号传送到横向曲线丘的核心。在该细胞核中，表达TACR1或GPR83的旋转孔隙（SPB）神经元的轴突，并且轴突终端的强近脊髓刺激的特异性亚核，突出了不同的逃避行为和自主响应。此外，表达GPR83的SPB神经元对皮肤机械刺激的高度敏感，并从高阈值和低阈值的主要机械感觉神经元接受强大的突触输入。值得注意的是，根据刺激强度，表达GPR83的SPB神经元的激活相关的益化性可以是正的或阴性的。这些发现揭示了SPB道的解剖学，生理学和功能明显的细分，使得触摸和疼痛的情感方面具有良好的情感方面。

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  • 来源
    《Nature》 |2020年第7833期|258-263|共6页
  • 作者

    Seungwon Choi; Junichi Hachisuka; Matthew A Brett; Alexandra R Magee; Yu Omori; Noor-Ul-Aine Iqbal; Dawei Zhang; Michelle M DeLisle; Rachel L Wolfson; Ling Bai; Celine Santiago; Shiaoching Gong; Martyn Goulding; Nathaniel Heintz; H Richard Koerber; Sarah E Ross; David D Ginty;

  • 作者单位

    Department of Neurobiology Howard Hughes Medical Institute Harvard Medical School;

    Department of Neurobiology University of Pittsburgh|Pittsburgh Center for Pain Research University of Pittsburgh|Institute of Neuroscience and Psychology University of Glasgow;

    Department of Neurobiology Howard Hughes Medical Institute Harvard Medical School;

    Department of Neurobiology Howard Hughes Medical Institute Harvard Medical School;

    Department of Neurobiology University of Pittsburgh|Pittsburgh Center for Pain Research University of Pittsburgh|Toray Industries Inc. Pharmaceutical Research Laboratories;

    Department of Neurobiology Howard Hughes Medical Institute Harvard Medical School;

    Department of Neurobiology Howard Hughes Medical Institute Harvard Medical School;

    Department of Neurobiology Howard Hughes Medical Institute Harvard Medical School;

    Department of Neurobiology Howard Hughes Medical Institute Harvard Medical School;

    Department of Neurobiology Howard Hughes Medical Institute Harvard Medical School;

    Department of Neurobiology Howard Hughes Medical Institute Harvard Medical School;

    The Laboratory of Molecular Biology Howard Hughes Medical Institute The Rockefeller University;

    Molecular Neurobiology Laboratory The Salk Institute for Biological Studies;

    The Laboratory of Molecular Biology Howard Hughes Medical Institute The Rockefeller University;

    Department of Neurobiology University of Pittsburgh|Pittsburgh Center for Pain Research University of Pittsburgh;

    Department of Neurobiology University of Pittsburgh|Pittsburgh Center for Pain Research University of Pittsburgh;

    Department of Neurobiology Howard Hughes Medical Institute Harvard Medical School;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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