Propofol decreases the excitability of cholinergic neurons in mouse basal forebrain via GABAA receptors
Propofol decreases the excitability of cholinergic neurons in mouse basal forebrain via GABAA receptors
复制标题
异丙酚通过 GABAA 受体降低小鼠基底前脑胆碱能神经元的兴奋性。
DOI：
10.1038/s41401-018-0168-6
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发表时间：
2019-06-01
影响因子：
8.2
通讯作者：
Wang, Lie-cheng
中科院分区：
文献类型：
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作者：
Chen, Lei;Yang, Zhi-lai;Wang, Lie-cheng
异丙酚是一种静脉麻醉剂，可激活γ-氨基丁酸A（GABA（A））受体并产生镇静催眠作用。异丙酚已被广泛应用于临床，以达到与人类睡眠相当的镇静作用。基底前脑（BF）是在睡眠-觉醒调节中起重要作用的脑区。以往的研究表明，丙泊酚通过BF影响睡眠-觉醒回路;然而，其机制仍不清楚。在目前的研究中，我们研究了异丙酚对胆碱能神经元的固有特性和他们的能力，兴奋性输入转换成尖峰在小鼠BF切片使用全细胞膜片钳记录的影响。异丙酚（10 μ M）的浴应用显着提高阈值电位（Vts），减少了响应于去极化电流注入的尖峰的数量，并增加了尖峰间期（ISI），能量屏障（Vts-Vrs），和绝对不应期（ARP）。这些作用通过共同应用GABA（A）受体拮抗剂印防己毒素（50 μ M）消除。总之，我们的研究结果表明，异丙酚通过GABAA受体降低小鼠BF胆碱能神经元的兴奋性。
Propofol is an intravenous anesthetic that can active gamma-aminobutyric acid A (GABA(A)) receptors and generate sedative-hypnotic effects. Propofol has been widely applied clinically to achieve sedation comparable to sleep in humans. The basal forebrain (BF) is a brain region that plays an important role in sleep-wake regulation. Previous studies suggest that propofol affects the sleep-wake circuit via the BF; however, the mechanism remains elusive. In the current study we investigated the effects of propofol on the inherent properties of cholinergic neurons and their ability to convert excitatory inputs into spikes in mouse BF slices using whole-cell patch clamp recordings. Bath application of propofol (10 mu M) significantly elevated the threshold potentials (Vts), decreased the number of spikes in response to a depolarizing current injection, and augmented the inter-spike intervals (ISIs), energy barrier (Vts-Vrs), and absolute refractory periods (ARPs). These effects were eliminated by co-application of a GABA(A) receptor antagonist picrotoxin (50 mu M). Altogether, our results reveal that propofol decreases the excitability of cholinergic neurons in mouse BF via GABAA receptors.