Mrgprd-expressing polymodal nociceptive neurons innervate most known classes of substantia gelatinosa neurons.
Mrgprd-expressing polymodal nociceptive neurons innervate most known classes of substantia gelatinosa neurons.
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DOI：
10.1523/jneurosci.3248-09.2009
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发表时间：
2009-10-21
期刊：
影响因子：
--
通讯作者：
Zylka MJ
中科院分区：
文献类型：
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作者：
Wang H;Zylka MJ
MAS相关的G蛋白偶联受体D（Mrgprd）标志着一个独特的感觉神经元的子集，从皮肤表皮到脊髓的胶状质（SG，板层II）传递多模态伤害性信息。此外，Mrgprd表达（Mrgprd+）神经元所需的机械，但不是热伤害性感受的充分表达。虽然这种解剖学和功能特异性表明Mrgprd+神经元可能与SG中的特定突触后靶点突触，但目前尚不清楚Mrgprd+神经元如何与脊髓回路相互作用。为了研究电路连接性，我们将光激活离子通道ChR-2-Venus（ChR 2-Venus）遗传靶向Mrgprd位点。在这些基因敲入小鼠中，ChR 2-Venus定位于非肽能Mrgprd+神经元和轴突，而肽能CGRP+神经元未被显著标记。从表达一个或两个拷贝的ChR 2-Venus的小鼠分离的Mrgprd+ DRG神经元可以在体外被激活，如通过光诱发电流和动作电位所证明的。此外，Mrgprd-ChR 2-Venus+脊髓切片中轴突终末的照明在一半的所有SG神经元中诱发兴奋性突触后电流（EPSC）。在这个子集内，Mrgprd+神经元单突触连接到大多数已知类别的SG神经元，包括放射状，紧张性中央，瞬时中央，垂直和天线细胞。这种细胞多样性排除了Mrgprd+神经元支配专门一类SG神经元的可能性。我们的研究结果设置了广泛的限制脊髓神经元的类型，处理传入输入Mrgprd+多模态伤害感受器。
The Mas-related G protein-coupled receptor D (Mrgprd) marks a distinct subset of sensory neurons that transmit polymodal nociceptive information from the skin epidermis to the substantia gelatinosa (SG, lamina II) of the spinal cord. Moreover, Mrgprd-expressing (Mrgprd+) neurons are required for the full expression of mechanical but not thermal nociception. While such anatomical and functional specificity suggests Mrgprd+ neurons might synapse with specific postsynaptic targets in the SG, precisely how Mrgprd+ neurons interface with spinal circuits is currently unknown. To study circuit connectivity, we genetically targeted the light-activated ion channel Channelrhodopsin-2-Venus (ChR2-Venus) to the Mrgprd locus. In these knock-in mice, ChR2-Venus was localized to nonpeptidergic Mrgprd+ neurons and axons, while peptidergic CGRP+ neurons were not significantly labeled. Dissociated Mrgprd+ DRG neurons from mice expressing one or two copies of ChR2-Venus could be activated in vitro as evidenced by light-evoked currents and action potentials. In addition, illumination of Mrgprd-ChR2-Venus+ axon terminals in spinal cord slices evoked excitatory postsynaptic currents (EPSCs) in half of all SG neurons. Within this subset, Mrgprd+ neurons were monosynaptically connected to most known classes of SG neurons, including radial, tonic central, transient central, vertical and antenna cells. This cellular diversity ruled out the possibility that Mrgprd+ neurons innervate a dedicated class of SG neuron. Our findings set broad constraints on the types of spinal neurons that process afferent input from Mrgprd+ polymodal nociceptors.