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首页> 外文期刊>Neuron >How Gastrin-Releasing Peptide Opens the Spinal Gate for Itch
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How Gastrin-Releasing Peptide Opens the Spinal Gate for Itch

机译：胃泌素释放肽如何为瘙痒打开脊柱

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摘要

Spinal transmission of pruritoceptive (itch) signals requires transneuronal signaling by gastrin-releasing peptide (GRP) produced by a subpopulation of dorsal horn excitatory interneurons. These neurons also express the glutamatergic marker vGluT2, raising the question of why glutamate alone is insufficient for spinal itch relay. Using optogenetics together with slice electrophysiology and mouse behavior, we demonstrate that baseline synaptic coupling between GRP and GRP receptor (GRPR) neurons is too weak for suprathreshold excitation. Only when we mimicked the endogenous firing of GRP neurons and stimulated them repetitively to fire bursts of action potentials did GRPR neurons depolarize progressively and become excitable by GRP neurons. GRPR but not glutamate receptor antagonism prevented this action. Provoking itch-like behavior by optogenetic activation of spinal GRP neurons required similar stimulation paradigms. These results establish a spinal gating mechanism for itch that requires sustained repetitive activity of presynaptic GRP neurons and postsynaptic GRP signaling to drive GRPR neuron output.
机译：瘙痒率（瘙痒）信号的脊柱透射需要通过胃泌素释放的肽（GRP）来传递传递信号传导，所述胃泌素释放肽（GRP）产生背角兴奋性间肠道潜力。这些神经元还表达了谷氨酸谷氨酸标记物VGlut2，提出了为什么谷氨酸单独的原因对脊柱瘙痒继电器不足。使用光源与切片电生理和鼠标行为一起，我们证明GRP和GRP受体（GRPR）神经元之间的基线突触耦合对于Suprathreshold激发而言太弱。只有当我们模仿GRP神经元的内源性射击并重复地刺激它们的火灾突发，才能逐渐消除GRPR神经元，并由GRP神经元变得激发。 GRPR但不是谷氨酸受体拮抗作用阻碍了这一行动。通过脊柱GRP神经元的致敏活化来激发瘙痒的行为需要类似的刺激范式。这些结果建立了瘙痒的脊柱门控机制，其需要持续的突触前GRP神经元和突触后GRP信号传递的持续重复活性，以驱动GRPR神经元输出。

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  • 来源
    《Neuron》 |2019年第1期|共21页
  • 作者

    Pagani Martina; Albisetti Gioele W.; Sivakumar Nandhini; Wildner Hendrik; Santello Mirko; Johannssen Helge C.; Zeilhofer Hanns Ulrich;

  • 作者单位

    Univ Zurich Inst Pharmacol &

    Toxicol Winterthurerstr 190 CH-8057 Zurich Switzerland;

    Univ Zurich Inst Pharmacol &

    Toxicol Winterthurerstr 190 CH-8057 Zurich Switzerland;

    Univ Zurich Inst Pharmacol &

    Toxicol Winterthurerstr 190 CH-8057 Zurich Switzerland;

    Univ Zurich Inst Pharmacol &

    Toxicol Winterthurerstr 190 CH-8057 Zurich Switzerland;

    Univ Zurich Inst Pharmacol &

    Toxicol Winterthurerstr 190 CH-8057 Zurich Switzerland;

    Univ Zurich Inst Pharmacol &

    Toxicol Winterthurerstr 190 CH-8057 Zurich Switzerland;

    Univ Zurich Inst Pharmacol &

    Toxicol Winterthurerstr 190 CH-8057 Zurich Switzerland;

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 神经病学;
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