Selective optogenetic activation of orexinergic terminals in the basal forebrain and locus coeruleus promotes emergence from isoflurane anaesthesia in rats
Selective optogenetic activation of orexinergic terminals in the basal forebrain and locus coeruleus promotes emergence from isoflurane anaesthesia in rats
复制标题
基底前脑和蓝斑中食欲素能末端的选择性光遗传学激活促进大鼠从异氟烷麻醉中苏醒。
DOI：
10.1016/j.bja.2020.09.037
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发表时间：
2021-01-05
影响因子：
9.8
通讯作者：
Dong, Hailong
中科院分区：
文献类型：
--
作者：
Wang, Dan;Guo, Yongxin;Dong, Hailong
背景资料：神经肽食欲素促进唤醒从全身麻醉，然而，神经回路介导的这种效果还没有被定义。我们研究了食欲素能神经元是否调节基底前脑（BF）和蓝斑（LC）从麻醉中出现。方法：使用基于CRISPR/Cas9的方法产生Hcrt（cre）大鼠。将编码光遗传学探针的病毒注射到下丘脑穹窿周围外侧（PeFLH）区，将光遗传学纤维包埋在PeFLH、BF或LC中，并测定在1.4vol %或0.8vol %异氟烷下麻醉状态的变化。在PeFLH中，98.8%（0.4%）的orexin-A阳性细胞表达tdTomato，91.9%（2.2%）的tdTomato细胞是orexin-A阳性的。在1.4vol%异氟醚麻醉下，与对照组相比，光遗传学激活PeFLH中食欲素能胞体的组的爆发抑制率较低，苏醒时间较短BF（937（122）vs 674（108）s，P= 0.0049）或LC（913 [128] vs 742 [76] s，P=0.022）中的食欲素能终末（923 [162] vs 493 [68] s，P= 0.0003）。光学刺激的orexinergic终端在BF和LC也提高了运动成绩的大鼠在0.8体积% isoflurane anaesthesia.Conclusions：orexinergic终端在FB或LC的激活介导的促进出现从麻醉orexinergic神经元在异氟烷麻醉。
Background: The neuropeptide orexin promotes arousal from general anaesthesia, however the neuronal circuits that mediate this effect have not been defined. We investigated whether orexinergic neurones modulate the basal forebrain (BF) and locus coeruleus (LC) in emergence from anaesthesia.Methods: Hcrt(cre) rats were generated using a CRISPR/Cas9-based approach. Viruses encoding optogenetic probes were injected into the perifornical lateral hypothalamic (PeFLH) area, optogenetic fibres were embedded in the PeFLH, BF, or LC, and changes in anaesthesia state under 1.4 vol% or 0.8 vol% isoflurane were determined.Results: In the PeFLH, 98.8% (0.4%) of orexin-A-positive cells expressed tdTomato, and 91.9% (2.2%) of tdTomato cells were orexin-A-positive. Under 1.4 vol% isoflurane anaesthesia, compared with control groups, burst suppression ratio was less, and emergence time was shorter in groups with optogenetic activation of orexinergic cell bodies in the PeFLH (923 [162] vs 493 [68] s, P=0.0003) or orexinergic terminals in the BF (937 (122) vs 674 (108) s, P=0.0049) or LC (913 [128] vs 742 [76] s, P=0.022). Optical stimulation of orexinergic terminals in the BF and LC also improved the movement scores of rats under 0.8 vol% isoflurane anaesthesia.Conclusions: Activation of orexinergic terminals in the FB or LC mediates facilitation of emergence from anaesthesia by orexinergic neurones during isoflurane anaesthesia.