Nociceptive information from the orofacial area projects to the trigeminal spinal subnucleus caudalis (Sp5C) and is then conveyed to several nuclei, including the parabrachial nucleus (PBN). The insular cortex (IC) receives orofacial nociceptive information and sends corticofugal projections to the Sp5C. The Sp5C consists of glutamatergic and GABAergic/glycinergic interneurons that induce EPSCs and IPSCs, respectively, in projection neurons. Therefore, quantification of glutamatergic IC inputs in combination with identifying postsynaptic neuronal subtypes is critical to elucidate IC roles in the regulation of Sp5C activities. We investigated features of synaptic transmission from the IC to glutamatergic and GABAergic/glycinergic Sp5C neurons of laminae I/II using VGAT-Venus transgenic rats that received an injection of AAV-ChR2-mCherry into the IC. Selective stimulation of IC axon terminals in Sp5C slice preparations induced monosynaptic EPSCs in both excitatory glutamatergic and inhibitory GABAergic/glycinergic Sp5C neurons with a comparable amplitude. Paired whole-cell patch-clamp recordings showed that unitary IPSCs from inhibitory neurons influencing excitatory neurons, including neurons projecting to the PBN, exhibited a high failure rate and were suppressed by both bicuculline and strychnine, suggesting that excitatory neurons in the Sp5C receive both GABAergic and glycinergic inhibition with low impact. Moreover, selective stimulation of IC axons increased the firing rate at the threshold responses. Finally, we demonstrated that selective stimulation of IC axons in the Sp5C by a chemogenetic approach decreased the thresholds of both mechanical and thermal nociception. Thus, IC projection to the Sp5C is likely to facilitate rather than suppress excitatory outputs from the Sp5C.

中文翻译：

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从岛叶皮质到三叉神经尾亚核的下降投射有利于大鼠臂旁核的兴奋性输出。

来自口面部区域的伤害性信息投射到三叉神经尾部亚核 (Sp5C)，然后传递到几个核团，包括臂旁核 (PBN)。岛叶皮质 (IC) 接收口面部伤害性信息并向 Sp5C 发送皮质投射。Sp5C 由谷氨酸能和 GABA 能/甘氨酸能中间神经元组成，它们分别在投射神经元中诱导 EPSC 和 IPSC。因此，谷氨酸能 IC 输入的量化与突触后神经元亚型的识别相结合对于阐明 IC 在 Sp5C 活性调节中的作用至关重要。我们使用在 IC 中注射 AAV-ChR2-mCherry 的 VGAT-Venus 转基因大鼠，研究了从 IC 到层板 I/II 的谷氨酸能和 GABA 能/甘氨酸能 Sp5C 神经元的突触传递特征。选择性刺激 Sp5C 切片制剂中的 IC 轴突末端可在兴奋性谷氨酸能和抑制性 GABA 能/甘氨酸能 Sp5C 神经元中诱导单突触 EPSC，其幅度相当。成对的全细胞膜片钳记录显示，来自影响兴奋性神经元（包括投射到PBN的神经元）的抑制性神经元的单一IPSC表现出很高的失败率，并且被荷包牡丹碱和马钱子碱抑制，这表明Sp5C中的兴奋性神经元同时接收GABA能和低影响的甘氨酸抑制。此外，IC 轴突的选择性刺激增加了阈值反应的放电率。最后，我们证明通过化学遗传学方法选择性刺激 Sp5C 中的 IC 轴突可降低机械和热伤害感受的阈值。因此，IC 投射到 Sp5C 可能会促进而不是抑制 Sp5C 的兴奋性输出。