Key Laboratory of Brain Science, Zunyi Medical University, Zunyi, China.
Department of Anesthesiology, Affiliated Hospital of Zunyi Medical University, Zunyi, China.
CNS Neurosci Ther. 2021 Jul;27(7):792-804. doi: 10.1111/cns.13635. Epub 2021 Mar 25.
The basal forebrain (BF) plays an essential role in wakefulness and cognition. Two subtypes of BF gamma-aminobutyric acid (GABA) neurons, including somatostatin-expressing (GABA ) and parvalbumin-positive (GABA ) neurons, function differently in mediating the natural sleep-wake cycle. Since the loss of consciousness induced by general anesthesia and the natural sleep-wake cycle probably share similar mechanisms, it is important to clarify the accurate roles of these neurons in general anesthesia procedure.
Based on two transgenic mouse lines expressing SOM-IRES-Cre and PV-IRES-Cre, we used a combination of genetic activation, inactivation, and chronic ablation approaches to further explore the behavioral and electroencephalography (EEG) roles of BF and BF neurons in general anesthesia. After a single intravenous injection of propofol and the induction and recovery times of isoflurane anesthesia, the anesthesia time was compared. The changes in cortical EEG under different conditions were also compared.
Activation of BF GABA neurons facilitates both the propofol and isoflurane anesthesia, manifesting as a longer anesthesia duration time with propofol anesthesia and a fast induction time and longer recovery time with isoflurane anesthesia. Moreover, BF GABA -activated mice displayed a greater suppression of cortical electrical activity during anesthesia, showing an increase in δ power bands or a simultaneous decrease in high-frequency power bands. However, only a limited and nuanced effect on propofol and isoflurane anesthesia was observed with the manipulated BF GABA neurons.
Our results suggested that BF GABA neurons play a critical role in propofol and isoflurane general anesthesia, while BF GABA neurons appeared to have little effect.
基底前脑(BF)在觉醒和认知中起着至关重要的作用。BF 中的两种γ-氨基丁酸(GABA)神经元亚型,包括生长抑素表达(GABA )和钙调蛋白结合蛋白阳性(GABA )神经元,在介导自然睡眠-觉醒周期方面发挥着不同的作用。由于全身麻醉诱导的意识丧失和自然睡眠-觉醒周期可能具有相似的机制,因此阐明这些神经元在全身麻醉过程中的准确作用非常重要。
基于两种表达 SOM-IRES-Cre 和 PV-IRES-Cre 的转基因小鼠系,我们使用基因激活、失活和慢性消融的组合方法,进一步探索 BF 和 BF 神经元在全身麻醉中的行为和脑电图(EEG)作用。在单次静脉注射异丙酚和异氟醚麻醉的诱导和恢复时间后,比较麻醉时间。还比较了不同条件下皮质 EEG 的变化。
激活 BF GABA 神经元可促进异丙酚和异氟醚麻醉,表现为异丙酚麻醉时麻醉时间延长,异氟醚麻醉时诱导时间加快,恢复时间延长。此外,BF GABA 激活的小鼠在麻醉期间表现出皮质电活动的更大抑制,表现为 δ 功率带增加或高频功率带同时降低。然而,操纵 BF GABA 神经元仅对异丙酚和异氟醚麻醉产生有限且细微的影响。
我们的结果表明,BF GABA 神经元在异丙酚和异氟醚全身麻醉中起着关键作用,而 BF GABA 神经元的作用似乎很小。