下丘脑外侧区-小脑顶核GABA能/Glu能神经环路在针刺预处理减轻心肌缺血再灌注损伤中的作用机制研究

针刺预处理可有效减轻心肌缺血再灌注损伤，但其神经环路调控机制尚不清楚。我们前期研究表明，针刺预处理可调节小脑顶核（FN）与下丘脑外侧区（LHA）神经元活动、GABA和Glu释放发挥心肌保护作用，但其具体机制有待进一步探明。神经科学研究显示，FN与LHA存在着直接的GABA能和Glu能纤维投射。据此，项目组提出“针刺预处理通过调控LHA-FN GABA能/Glu能神经环路，并经交感神经途径发挥心肌保护作用”的假说，拟应用特定神经元荧光转基因小鼠，明确LHA-FN中GABA能/Glu能神经元在针刺效应中的作用；采用病毒示踪和光遗传技术进一步确证该神经环路中何种类型神经投射是针刺效应机制的主要调控靶点；结合化学遗传和电生理技术初步探明LHA-FN中GABA能/Glu能神经元在针刺效应机制中是否存在交互作用，是否通过交感神经途径参与针刺效应，为从神经环路调控角度阐释针刺效应机制提供新的证据和支持。

Acupuncture pretreatment has an obviously effect on improving the myocardial ischemia-reperfusion injury, but the regulation mechanism of neural circuits is not clear. Our previous studies have shown that acupuncture pretreatment playing a role in myocardial protection by regulating the activity of neurons in the fastigial nucleus (FN) and the lateral hypothalamic area (LHA), and the release of GABA and Glu, but its mechanism needs to be further explored. Neuroscience research has shown that there are direct GABA and Glu projections between FN and LHA. Therefore, we propose the hypothesis that acupuncture pretreatment can regulate the LHA-FN GABAergic/glutamatergic neural circuit and participate in the regulation of the cardiac function through the sympathetic pathway. In this study, we intend to clarify the role of GABAergic/glutamatergic neurons of LHA-FN in acupuncture effect by using specific neuron fluorescent transgenic mice, and further confirm which type of neural projection of this neural circuits is the main regulatory target of acupuncture effect mechanism by using virus tracing and photogenetic technology. In addition, whether there is an interactive regulation mode of GABAergic/glutamatergic neurons of LHA-FN in the mechanism of acupuncture effect and whether they participate in the acupuncture effect through sympathetic pathway by combining chemical genetics with electrophysiology. This study will provide new evidence and support for the explanation of acupuncture effect mechanism from the perspective of neural circuit regulation.