SCN区NMS+神经元激活DMH参与单色蓝光促七氟烷麻醉觉醒的细胞和神经环路机制

老龄患者术后苏醒延迟常见，目前尚无特效药物或干预措施，可安全高效地用于促进全麻苏醒。单色蓝光通过激活SCN脑区发挥促觉醒效应，显著缩短小鼠七氟烷麻醉苏醒时间，目前尚不清楚其发挥促觉醒效应的具体细胞和神经环路机制。根据前期研究和神经解剖学我们提出假说：单色蓝光促发七氟烷麻醉觉醒的机制，可能是通过兴奋SCN脑区NMS+神经后抑制SPZ脑区GABA能神经元，使DMH谷氨酸能神经元脱抑制激活，经DMH-LH的神经投射实现促觉醒效应。本研究将利用转基因动物模型，采用在体电生理记录、光遗传学和化学遗传学、膜片钳等技术，以SCN脑区NMS+神经元投射为切入点，明确蓝光激活SCN脑区NMS+神经元经SPZ投射，调控DMH脑区谷氨酸能神经元的细胞和神经环路机制，以及DMH谷氨酸能神经脱抑制激活后，促七氟烷麻醉觉醒的效果。通过上述研究为蓝光促觉醒效应提供理论解释，并为临床开发促发全麻苏醒的干预措施提供新思路。

Delayed postoperative recovery is common in elderly surgical patients, currently there is no specific drug or interventions that can be safely and efficiently used routinely to promote the recovery of general anesthesia in geriatric patients. Monochromatic blue light can significantly shorten the recovery time of sevoflurane anesthesia by activating the SCN neurons in mice. According to our previous research and based on knowledge of neuroanatomy, we propose the hypothesis about the cellular and neural circuit mechanism of monochromatic blue light induced awakening in sevoflurane anesthesia: by stimulating NMS+ neurons in SCN area, monochromatic blue light will inhibit GABAergic neurons in SPZ region, thus will disinhibit and activate the glutamatergic neurons in DMH, finally induce awakening through the neural projection from DMH to LH. In this study, using transgenic animal model, with the help of in vivo electrophysiological recording, optogenetics and chemical genetics techniques, whole cell patch clamp and other technologies, we plan to explore the projection of blue light sensitive NMS+ neurons in SCN, to clarify how can NMS+ cells induce the disinhibition of DMH glutamatergic neuron through projection from SPZ, and promote awakening in sevoflurane anesthesia. The above study will provide a theoretical explanation for the effect of blue light induced arousal, and provides a new idea for the development of intervention to promote the recovery of general anesthesia in geriatric surgical patients.