海马TASK离子通道介导脑电theta波和尖波波纹涉及吸入麻醉药致遗忘作用机制

非预期的麻醉中意识即术中知晓与术中记忆密切相关，是一种严重并发症，可引起严重的情感和精神健康问题，但其机制未明，且缺乏预防和监测方法。临床观察发现吸入麻醉比静脉麻醉术中知晓发生率低。海马是学习记忆的重要脑区，在前期国家自然科学基金支持下，我们初步研究发现七氟醚吸入麻醉明显诱导脑电theta波，而海马theta波与记忆功能密切相关。TASK离子通道是高表达于海马区的一种双孔背景钾通道，其被证实参与theta波和尖波波纹形成，吸入麻醉药七氟醚激活TASK离子通道，抑制细胞兴奋性，而静脉麻醉药丙泊酚对TASK离子通道影响轻微。本申请基于我们初步研究结果和上述背景分析，提出吸入麻醉药激动海马TASK离子通道调节脑电theta波及记忆。本课题设计应用基因敲除小鼠、神经电生理、光遗传等技术验证上述假设,揭示吸入麻醉药调节海马theta波和尖波波纹致遗忘机制，为全麻药致遗忘作用及临床应用研究提供理论参考。

Unanticipated awareness during anesthesia, which is related to intraoperative memory, is a serious complication, which can cause serious emotional and mental health problems, but its mechanism is not clear, and there is a lack of prevention and monitoring methods. Clinical observation showed that the incidence of awareness during inhalation anesthesia was lower than that during intravenous anesthesia. Hippocampus is an important area of learning and memory. With the support of previous NSFC, our preliminary study found that under sevoflurane inhalational anesthesia, theta wave of EEG was significantly activated. Theta wave in hippocampus has been reported to be related to memory. A two pore background potassium channel TASK with high expression in the hippocampus was confirmed to be involved in the formation of theta wave and sharp wave ripples. Sevoflurane, an anesthetic, was inhaled to potentially activate the TASK channel and inhibit cell excitability, while propofol, an intravenous anesthetic, had little effect on the channel. Based on our preliminary research results and the above background analysis, this proposal proposes that inhaling anesthetics can regulate theta waves and memory by activating the hippocampal TASK ion channel. In this study, gene knockout mice, neuroelectrophysiology and photogenetics were used to verify the above hypotheses and to reveal the mechanism of inhaling anesthetics to regulate theta waves and sharp wave ripples in hippocampus and amnesia, which will provide theoretical reference for the research and clinical application of amnesia caused by general anesthetics.