The roles of serotonergic and noradrenergic signaling in nociceptive processing in the central nervous system are well known. However, dopaminergic signaling is also relevant to various physical functions, including nociception. The zona incerta is a subthalamic nucleus in which the A13 dopaminergic cell group resides, but how this A13 group affects nociceptive processing remains unknown. Recently, we showed that acute nociceptive stimuli rapidly induce the activity of A10 (ventral tegmental area) dopamine neurons via fiber photometry. In this study, we measured the activity of A13 dopaminergic neurons in response to acute nociceptive stimuli using the same system. Adeno-associated viruses (AAV-CAG-FLEX-G-CaMP6 and AAV-CAG-FLEX-mCherry) were unilaterally injected into the A13 site in transgenic mice carrying a dopamine transporter promotor-regulated Cre recombinase transgene to specifically introduce G-CaMP6/mCherry into A13 dopaminergic cell bodies through site-specific infection. We measured G-CaMP6/mCherry fluorescence intensity in the A13 site to acute nociceptive stimuli (pinch stimulus and heat stimulus). These stimuli significantly induced a rapid increase in G-CaMP6 fluorescence intensity, but non-nociceptive control stimuli did not. In contrast, mCherry fluorescence intensity was not significantly changed by nociceptive stimuli or non-nociceptive stimuli. Our finding is the first report to measure the activity of A13 dopaminergic neurons to aversive stimuli. A13 dopaminergic neurons project to the periaqueductal gray and the central nucleus of the amygdala, which are both well known as key regions in nociceptive processing. Therefore, together with our A10 study, our results indicate that A13 dopaminergic neurons play important roles in nociceptive processing.

中文翻译：

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位于伤害性透明带中的A13多巴胺能神经元参与伤害性处理：纤维光度法研究。

血清素能和去甲肾上腺素能信号传导在中枢神经系统的伤害感受过程中的作用是众所周知的。但是，多巴胺能信号传导也与包括伤害感受在内的各种物理功能有关。不透明带是A13多巴胺能细胞群所在的丘脑下核，但该A13群如何影响伤害感受尚不清楚。最近，我们显示了急性伤害性刺激可以通过纤维光度法快速诱导A10（腹侧被盖区）多巴胺神经元的活性。在这项研究中，我们使用相同的系统测量了A13多巴胺能神经元对急性伤害感受性刺激的反应。将腺相关病毒（AAV-CAG-FLEX-G-CaMP6和AAV-CAG-FLEX-mCherry）单方面注射到携带多巴胺转运蛋白启动子调控的Cre重组酶转基因的转基因小鼠的A13位点中，专门引入G-CaMP6 / mCherry通过位点特异性感染进入A13多巴胺能细胞体。我们在急性伤害性刺激（夹点刺激和热刺激）的A13部位测量了G-CaMP6 / mCherry荧光强度。这些刺激显着诱导了G-CaMP6荧光强度的快速增加，但非伤害性对照刺激却没有。相反，伤害性刺激或非伤害性刺激未显着改变mCherry荧光强度。我们的发现是第一个测量A13多巴胺能神经元对厌恶刺激活性的报告。A13多巴胺能神经元投射到杏仁核的导水管周围灰色和中央核，这两个都是众所周知的伤害性加工关键区域。因此，与我们的A10研究一起，我们的结果表明A13多巴胺能神经元在伤害感受过程中起重要作用。