终纹床核-中央杏仁核CRH信号对七氟烷诱导的幼年小鼠记忆损伤的调控作用及机制研究

全身麻醉药对未成熟大脑智力发育的影响一直是社会关注的重要问题，而目前关于幼年麻醉经历对后续学习记忆的影响及机制尚不清楚。我们发现幼年小鼠多次七氟烷暴露会引起长时记忆损伤，多次七氟烷暴露减轻终纹床核CRH-ERK信号的激活，而阻断该信号可缓解记忆损伤。故假设：多次七氟烷暴露通过抑制幼年小鼠终纹床核-中央杏仁核环路CRH神经元CRH-ERK信号，减弱GABA能突触传递损伤长时记忆。我们通过建立幼年小鼠多次麻醉暴露模型，联合巴甫洛夫恐惧条件化行为范式，明确多次七氟烷暴露损伤长时记忆。使用行为学、药理学、化学遗传学、环路示踪和离体脑片电生理等技术，探讨终纹床核-中央杏仁核环路CRH神经元CRH-ERK信号在多次七氟烷暴露引起幼年小鼠长时记忆损伤中的作用。本研究将拓展公众对麻醉药物影响幼年神经发育的认识，为改善临床麻醉预后及围术期临床决策提供新的理论依据。

The impact of general anesthetics on immature brain has always been an important issue of social concern. However, the effect of the anesthesia experience in childhood on subsequent learning and memory and its mechanism are still unclear. We found that multiple exposure of sevoflurane in juvenile mice can cause long-term memory impairment. Multiple sevoflurane exposures reduce the activation of CRH-ERK signal in the nucleus of the stria terminalis, and blocking this signal can alleviate memory impairment. Therefore, we hypothesized that multiple exposures of sevoflurane may impair long-term memory by attenuating GABAgeric transmission through inhibiting the CRH-ERK signal of the CRH neuron in the BNST-CeA pathway in juvenile mice. We established multiple anesthesia exposures model in juvenile mice, combined with Palov’s Fear-Conditioning paradigm, to clarify that multiple sevoflurane exposures impairs long term memory. we use behavior test, pharmacological methods, chemogenetics, neural tracing, in vitro brain slice electrophysiology and other techniques to explore the role of the CRH-ERK signal of CRH neuron in the BNST-CeA pathway in the development of memory impairment induced by multiple sevoflurane exposures in juvenile mice. This study will expand the public's understanding of the effect of anesthetics on the neurodevelopment of young children, and provide new theoretical basis for improving the prognosis of clinical anesthesia and better perioperative clinical decision-making.