Background

The cellular and molecular mechanisms by which general anaesthesia occurs is poorly understood. Hippocampal interneurone subpopulations, which are critical regulators of cognitive function, have diverse neurophysiological and synaptic properties, but their responses to anaesthetics are unclear.

Methods

We used live-cell imaging of fluorescent biosensors expressed in mouse hippocampal neurones to delineate interneurone subtype-specific effects of isoflurane on synaptic vesicle exocytosis. The role of voltage-gated sodium channel (Na_v) subtype expression in determining isoflurane sensitivity was probed by overexpression or knockdown of specific Na_v subtypes in identified interneurones.

Results

Clinically relevant concentrations of isoflurane differentially inhibited synaptic vesicle exocytosis: to 83.1% (11.7%) of control in parvalbumin-expressing interneurones, and to 58.6% (13.3%) and 64.5% (8.5%) of control in somatostatin-expressing interneurones and glutamatergic neurones, respectively. The relative expression of Na_v1.1 (associated with lower sensitivity) and Na_v1.6 (associated with higher sensitivity) determined the sensitivity of exocytosis to isoflurane.

Conclusions

Isoflurane inhibits synaptic vesicle exocytosis from hippocampal glutamatergic neurones and GABAergic interneurones in a cell-type-specific manner depending on their expression of voltage-gated sodium channel subtypes.

中文翻译：

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挥发性麻醉剂异氟醚选择性抑制小鼠海马中间神经元亚型释放γ-氨基丁酸

背景

全身麻醉发生的细胞和分子机制知之甚少。海马中间神经元亚群是认知功能的关键调节因子，具有多种神经生理学和突触特性，但它们对麻醉剂的反应尚不清楚。

方法

我们使用在小鼠海马神经元中表达的荧光生物传感器的活细胞成像来描述异氟醚对突触小泡胞吐作用的神经元间亚型特异性影响。电压门控钠通道 (Na _v ) 亚型表达在确定异氟醚敏感性中的作用是通过在确定的中间神经元中过表达或敲低特定 Na _v亚型来探讨的。

结果

异氟醚的临床相关浓度差异抑制突触小泡胞吐作用：在表达小白蛋白的中间神经元中达到对照的 83.1% (11.7%)，在表达生长抑素的中间神经元和谷氨酸能中达到对照的 58.6% (13.3%) 和 64.5% (8.5%)神经元，分别。_{Na v} 1.1（与较低敏感性相关）和 Na _v 1.6（与较高敏感性相关）的相对表达决定了胞吐作用对异氟醚的敏感性。

结论

根据电压门控钠通道亚型的表达，异氟醚以细胞类型特异性方式抑制海马谷氨酸能神经元和 GABA 能中间神经元的突触小泡胞吐作用。