A Neural Circuit from the Paraventricular Thalamus to the Bed Nucleus of the Stria Terminalis for the Regulation of States of Consciousness during Sevoflurane Anesthesia in Mice
A Neural Circuit from the Paraventricular Thalamus to the Bed Nucleus of the Stria Terminalis for the Regulation of States of Consciousness during Sevoflurane Anesthesia in Mice
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从室旁丘脑到终纹床核的神经回路用于调节小鼠七氟烷麻醉期间的意识状态
DOI：
10.1097/aln.0000000000004195
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发表时间：
2022-03
期刊：
影响因子：
8.8
通讯作者：
Wei Mei
中科院分区：
文献类型：
--
作者：
Jia-Yan Li;Shao-Jie Gao;Ran-Ran Li;Wei Wang;Jia Sun;Long-Qing Zhang;Jia-Yi Wu;Dai-Qiang Liu;Pei Zhang;Bo Tian;Wei Mei
背景：七氟醚诱导的意识调节背后的神经回路尚不清楚。本研究假设终纹通路的室旁丘脑床核在七氟醚麻醉时的意识状态调节中起重要作用。方法：采用狂犬病毒跨突触示踪技术，揭示从室旁丘脑到终纹床核的神经通路。本研究采用化学遗传学和光遗传学方法结合皮质脑电图记录研究了该通路在七氟醚麻醉诱导、维持和苏醒中的作用。本研究使用了雄性和雌性小鼠。结果：终末纹床核γ-氨基丁酸介导的神经元和谷氨酸能神经元均接受室旁丘脑谷氨酸能投射。室旁丘脑谷氨酸能神经元的化学发生抑制延长了七氟醚麻醉苏醒时间（hm4d -氯氮平n -氧化物比mcherry -氯氮平n -氧化物，分别为281±88比172±48 s， P < 0.001, n = 24），缩短了诱导时间（101±32比136±34 s， P = 0.002, n = 24）；以及七氟醚麻醉下翻正反射丧失或恢复的ec50（50%小鼠失去翻正反射的浓度的平均[95% CI]为1.16[1.12至1.20]vs. 1.49[1.46至1.53]vol%, P < 0.001, n = 20； 50%小鼠恢复翻正反射的浓度为0.95[0.86至1.03]vs. 1.34[1.29至1.40]vol%, P < 0.001, n = 20）。在抑制室旁丘脑床终末核纹通路时也观察到类似的结果。光遗传激活该途径产生相反的效果。此外，该通路的短暂刺激在七氟醚连续稳态全身麻醉期间有效地诱导了行为唤醒，并在七氟醚诱导的爆发抑制期间减少了麻醉深度。结论：小鼠在七氟醚麻醉时，从室旁丘脑神经元到终纹床核的轴突投射参与了意识状态的调节。小鼠丘脑室旁谷氨酸能神经元投射到终纹床核的化学发生抑制减少了七氟醚麻醉诱导时间并延长了苏醒时间，而激活该途径则具有相反的效果。这些观察结果表明，室旁丘脑的谷氨酸能神经元通过向终纹床核的投射参与了七氟烷麻醉的作用机制。
Background: The neural circuitry underlying sevoflurane-induced modulation of consciousness is poorly understood. This study hypothesized that the paraventricular thalamus bed nucleus of the stria terminalis pathway plays an important role in regulating states of consciousness during sevoflurane anesthesia. Methods: Rabies virus–based transsynaptic tracing techniques were employed to reveal the neural pathway from the paraventricular thalamus to the bed nucleus of the stria terminalis. This study investigated the role of this pathway in sevoflurane anesthesia induction, maintenance, and emergence using chemogenetic and optogenetic methods combined with cortical electroencephalogram recordings. Both male and female mice were used in this study. Results: Both γ-aminobutyric acid–mediated and glutamatergic neurons in the bed nucleus of the stria terminalis receive paraventricular thalamus glutamatergic projections. Chemogenetic inhibition of paraventricular thalamus glutamatergic neurons prolonged the sevoflurane anesthesia emergence time (mean ± SD, hM4D–clozapine N-oxide vs. mCherry–clozapine N-oxide, 281 ± 88 vs. 172 ± 48 s, P < 0.001, n = 24) and decreased the induction time (101 ± 32 vs. 136 ± 34 s, P = 0.002, n = 24), as well as the EC5 0 for the loss or recovery of the righting reflex under sevoflurane anesthesia (mean [95% CI] for the concentration at which 50% of the mice lost their righting reflex, 1.16 [1.12 to 1.20] vs. 1.49 [1.46 to 1.53] vol%, P < 0.001, n = 20; and for the concentration at which 50% of the mice recovered their righting reflex, 0.95 [0.86 to 1.03] vs. 1.34 [1.29 to 1.40] vol%, P < 0.001, n = 20). Similar results were observed during suppression of the paraventricular thalamus bed nucleus–stria terminalis pathway. Optogenetic activation of this pathway produced the opposite effects. Additionally, transient stimulation of this pathway efficiently induced behavioral arousal during continuous steady-state general anesthesia with sevoflurane and reduced the depth of anesthesia during sevoflurane-induced burst suppression. Conclusions: In mice, axonal projections from the paraventricular thalamic neurons to the bed nucleus of the stria terminalis contribute to regulating states of consciousness during sevoflurane anesthesia. Chemogenetic inhibition of paraventricular glutamatergic neurons in the mouse thalamus projecting to the bed nucleus of the stria terminalis reduced induction time and prolonged emergence from sevoflurane anesthesia, while activation of this pathway had opposite effects. These observations suggest that glutamatergic neurons of the paraventricular thalamus contribute to the mechanisms of actions of sevoflurane anesthesia via their projections to the bed nucleus of the stria terminalis.
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