Propofol downregulates the activity of glutamatergic neurons in the basal forebrain via affecting intrinsic membrane properties and postsynaptic GABAARs.
Propofol downregulates the activity of glutamatergic neurons in the basal forebrain via affecting intrinsic membrane properties and postsynaptic GABAARs.
复制标题
异丙酚通过影响内在膜特性和突触后 GABAAR 下调基底前脑谷氨酸能神经元的活性。
DOI：
10.1097/wnr.0000000000001540
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发表时间：
2020
期刊：
影响因子：
1.7
通讯作者：
Cui Jian
中科院分区：
文献类型：
--
作者：
Li Yuping;Chen Lin;Zhu Dan;Chen Yaohua;Qin Wanxiang;Cui Jian
异丙酚麻醉迅速导致意识丧失，而这种现象背后的神经机制仍不清楚。基底前脑的谷氨酸能神经元在觉醒的启动和维持中起重要作用。在这里，我们选择性地记录了vGlut-2-Cre小鼠中谷氨酸能神经元的活动。异丙酚以浓度依赖性方式诱导外向电流。浴应用异丙酚产生膜超极化和抑制这些神经元的放电率。异丙酚诱导的稳定外向电流持续后，阻断的动作电位，这意味着直接的突触后效应异丙酚。异丙酚通过影响GABA受体选择性地增加GABA能抑制性突触传入，但不影响多巴胺能传递。异丙酚通过直接影响膜的固有特性和抑制性突触传递抑制多巴胺能神经元的兴奋性。这种抑制作用可能为异丙酚的麻醉作用提供了新的机制。
Propofol anesthesia rapidly causes loss of consciousness, while the neural mechanism underlying this phenomenon is still unclear. Glutamatergic neurons in the basal forebrain play an important role in initiation and maintenance of wakefulness. Here, we selectively recorded the activity of glutamatergic neurons in vGlut-2-Cre mice. Propofol induced outward currents in a concentration-dependent manner. Bath application of propofol generated membrane hyperpolarization and suppressed the firing rates in these neurons. Propofol-induced stable outward currents persisted after blockade of the action potentials, implying a direct postsynaptic effect of propofol. Furthermore, propofol selectively increased the GABAergic inhibitory synaptic inputs via affecting the GABA A Rs, but did not affect the glutamatergic transmissions. Together, propofol inhibits the excitability of the glutamatergic neurons via direct influencing the membrane intrinsic properties and the inhibitory synaptic transmission. This inhibitory effect might provide a novel mechanism for the propofol-induced anesthesia.