BACKGROUND Surgery can induce severe neuroinflammation and negative emotional symptoms, such as anxiety-like behaviour. We studied whether reactive astrocytes in the zona incerta (ZI) mediate surgery-induced anxiety in mice. METHODS Laparotomy under isoflurane 1.5 vol% was used as a model in adult mice. The role of the ZI in surgery-induced anxiety was evaluated by behavioural tests, optical fibre recordings of neuronal activity, in vivo electrophysiological recordings, chemogenetics, and optogenetics. RESULTS Operative mice showed increased anxiety-like behaviour. Immunostaining and optical calcium recording revealed that astrocytes were abnormally activated in the ZI. Pharmacologic (F3, 15=5.837, P=0.044) or genetic manipulation (open field test: t7.41=3.66, P=0.007; elevated plus maze [EPM]: t10=2.70, P=0.022) of astrocyte activation in the ZI relieved anxiety-like behaviour in surgery-treated mice. Compared with the sham group, the surgery group showed increased extrasynaptic GABA concentrations and decreased GABA transporter-3 (GAT-3) expression, and inactivation of GABAergic neurones in the ZI. Upregulating GAT-3 in ZI astrocytes (OFT: t10.83=2.91, P=0.014; EPM: t9.15=3.55, P=0.006) or activating the GABAergic projection from ZI to the median raphe nucleus (ZIGABA→median raphe nucleus) (EPM: entries: F1, 24=3.45, P=0.027; time: F1, 25=4.07, P=0.043) ameliorated surgery-induced anxiety. CONCLUSIONS Reactive astrocytes in the zona incerta mediate surgery-induced anxiety, possibly by regulating GAT-3-mediated GABA homeostasis and inactivating ZIGABA→median raphe nucleus projections in mice.

中文翻译：

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反应性星形胶质细胞通过调节小鼠不定带中的 GABA 能信号介导术后手术诱导的焦虑。


背景 手术会诱发严重的神经炎症和负面的情绪症状，例如焦虑样行为。我们研究了不定带 （ZI） 中的反应性星形胶质细胞是否介导小鼠手术诱导的焦虑。方法 使用异氟醚 1.5 vol% 下的剖腹手术作为成年小鼠的模型。通过行为测试、神经元活动的光纤记录、体内电生理记录、化学遗传学和光遗传学评估 ZI 在手术诱导的焦虑中的作用。结果手术小鼠表现出增加的焦虑样行为。免疫染色和光学钙记录显示星形胶质细胞在 ZI 中异常激活。ZI 中星形胶质细胞活化的药理学 （F3， 15=5.837， P=0.044） 或基因操作 （旷场试验： t7.41=3.66，P=0.007;高架加迷宫 [EPM]： t10=2.70，P = 0.022） 缓解了手术治疗小鼠的焦虑样行为。与假手术组相比，手术组突触外 GABA 浓度增加，GABA 转运蛋白 3 （GAT-3） 表达降低，ZI 中 GABA 能神经元失活。在 ZI 星形胶质细胞中上调 GAT-3 （OFT： t10.83=2.91，P=0.014;EPM：t9.15=3.55，P=0.006）或激活从 ZI 到中缝核 （ZIGABA→正中缝核） 的 GABA 能投射（EPM：条目：F1,24=3.45，P=0.027;时间：F1,25=4.07，P=0.043）改善了手术引起的焦虑。结论 不定带中的反应性星形胶质细胞介导手术诱导的焦虑，可能是通过调节 GAT-3 介导的 GABA 稳态和灭活小鼠 ZIGABA→ 正中缝核投射。