Spinal Neuropeptide Y1 Receptor-Expressing Neurons Form an Essential Excitatory Pathway for Mechanical Itch
Spinal Neuropeptide Y1 Receptor-Expressing Neurons Form an Essential Excitatory Pathway for Mechanical Itch
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DOI：
10.1016/j.celrep.2019.06.033
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发表时间：
2019-07-16
期刊：
影响因子：
8.8
通讯作者：
Goulding, Martyn
中科院分区：
文献类型：
--
作者：
Acton, David;Ren, Xiangyu;Goulding, Martyn
急性瘙痒可由化学或机械刺激产生，其激活外周和脊髓中的单独通路。虽然在绘制化学性瘙痒的传播途径方面已经取得了实质性进展，但机械性瘙痒的中枢途径仍然不清楚。使用互补的遗传和药理学操作，我们表明，兴奋性神经元标记的神经肽Y1受体（Y1（Cre）神经元）的表达形成一个必不可少的途径，在脊髓背侧的机械，而不是化学瘙痒的传输。抑制或沉默Y1（Cre）神经元消除机械性瘙痒，而化学发生激活诱导抓挠。此外，使用Y1条件性基因敲除小鼠，我们表明，内源性神经肽Y（NPY）的行为，通过背角Y1表达神经元，以抑制光点状触摸和机械瘙痒刺激。因此，NPY-Y1信号传导通过建立触摸辨别和机械瘙痒反射的生物学相关阈值来调节无害触觉信息的传输。
Acute itch can be generated by either chemical or mechanical stimuli, which activate separate pathways in the periphery and spinal cord. While substantial progress has been made in mapping the transmission pathway for chemical itch, the central pathway for mechanical itch remains obscure. Using complementary genetic and pharmacological manipulations, we show that excitatory neurons marked by the expression of the neuropeptide Y1 receptor (Y1(Cre) neurons) form an essential pathway in the dorsal spinal cord for the transmission of mechanical but not chemical itch. Ablating or silencing the Y1(Cre) neurons abrogates mechanical itch, while chemogenetic activation induces scratching. Moreover, using Y1 conditional knockout mice, we demonstrate that endogenous neuropeptide Y (NPY) acts via dorsal-horn Y1-expressing neurons to suppress light punctate touch and mechanical itch stimuli. NPY-Y1 signaling thus regulates the transmission of innocuous tactile information by establishing biologically relevant thresholds for touch discrimination and mechanical itch reflexes.