Involvement of A13 dopaminergic neurons located in the zona incerta in nociceptive processing: a fiber photometry study
Involvement of A13 dopaminergic neurons located in the zona incerta in nociceptive processing: a fiber photometry study
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DOI：
10.1186/s13041-020-00600-w
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发表时间：
2020-04-14
期刊：
影响因子：
3.6
通讯作者：
Kuwaki, Tomoyuki
中科院分区：
文献类型：
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作者：
Moriya, Shunpei;Yamashita, Akira;Kuwaki, Tomoyuki
5-羟色胺能和去甲肾上腺素能信号在中枢神经系统的伤害性信息处理中的作用是众所周知的。然而，多巴胺能信号也与包括伤害性感受在内的各种生理功能有关。未确定带是丘脑底核，A13多巴胺能细胞群位于其中，但该A13群如何影响伤害性信息处理仍不清楚。最近，我们通过纤维光度法研究了急性伤害性刺激对腹侧被盖区多巴胺神经元的激活作用。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性刺激的反应。将腺相关病毒(AAV-CAG-FLEX-G-CAMP6和AAV-CAG-FLEX-mCherry)单侧注射到携带多巴胺转运子启动子调控的Cre重组酶转基因小鼠的A13部位，通过部位特异性感染将G-CaMP6/mCherry特异性地导入A13多巴胺能细胞。我们测量了急性伤害性刺激(挤压刺激和热刺激)下A13区G-CaMP6/mCherry的荧光强度。这些刺激可显著增加G-CaMP6的荧光强度，而非伤害性对照刺激则无此作用。伤害性刺激和非伤害性刺激对mCherry的荧光强度无明显影响。我们的发现是第一次测量A13多巴胺能神经元对厌恶刺激的活动。A13多巴胺能神经元投射到中脑导水管周围灰质和杏仁中央核，这两个区域都是众所周知的伤害性加工的关键区域。因此，结合我们的A10研究，我们的结果表明A13多巴胺能神经元在伤害性信息处理中发挥重要作用。
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.