心血管调控对于维持血压稳态有重要的生理意义。高血压是一种常见的心血管疾病，其发病机制至今尚未阐明，但自主神经调控紊乱在高血压发病中起着重要作用。孤束核是动脉压力感受器传入的初级中继站和整合中枢，参与动脉血压的调控。中枢神经系统表达苯乙胺-N-甲基转移酶（PNMT）的肾上腺素能神经元参与多种生理功能，其中延髓腹外侧头端区的PNMT神经元可直接调控交感神经活动而影响动脉血压，但孤束核PNMT神经元的的生理学作用及其环路联系尚未阐明。本课题拟应用多学科前沿技术，揭示孤束核PNMT神经元参与心血管调节的环路机制。为此，我们将观察选择性激活或损毁孤束核PNMT神经元对心血管活动的影响；解析PNMT的环路联系和突触传递的分子机制；分析PNMT神经元的生物化学表型。这些研究结果将有助于理解动脉血压中枢调控的基础环路，为开发中枢性抗高血压药物提供分子水平的靶点。

Hypertension is one of the most common cardiovascular diseases and its pathogenic mechanism remains incompletely understood. It is generally accepted that autonomic dysfunction apparently contributes to the onset and development of hypertension. Nucleus tractus solitarii (NTS) is the first relay center of arterial baroreceptors and therefore plays a crucial role in regulation of blood pressure. The central adrenergic neurons, expressing phenylethanolamine N-methyl transferase (PNMT), exert multiple physiological functions. It has been demonstrated that PNMT neuron located in the rostral ventrolateral medulla is capable of affecting blood pressure via direct control of sympathetic output. However the physiological role of PNMT neurons in the NTS and its circuit basis is little known to date. With multidisciplinary approaches, the present project is aimed to underpin the circuit mechanism responsible for the modulation of cardiovascular activity. To this end, we will seek to determine whether selective activation or lesion of PNMT neurons in the NTS affects cardiovascular activity, to carry out genetic dissection of PNMT neuronal circuits and reveal molecular mechanism of synaptic transmission, and finally to analyze biochemical phenotypes of these neurons. These results would be expected to help better understand the circuit mechanism of controlling blood pressure and provide central molecular targets of anti-hypertensive drugs.