Exploring sympathetic neuronal discharge patterns communicating homeostatic cardiovascular adjustments in humans

我的长期目标是产生关于人类心血管系统交感神经调节的知识。为了让人类在生理压力下（如体育锻炼或站立）保持活力，交感神经系统会传达心血管调节信息，以确保最佳的血压和血流量。为了做到这一点，交感神经系统依靠不同大小的神经元向循环传递精确的神经信息，即动作电位（ap）。利用微神经摄影技术研究人类交感AP放电模式，我们了解了交感神经系统用于沟通心血管调节的基本神经元放电和募集策略。然而，新的发现挑战了我们对交感AP放电模式和调节这些放电模式的机制的基本理解，突出表明我们对交感AP放电的认识仍处于起步阶段。因此，我的研究计划的长期目标是推进我们对交感AP亚群放电的理解，它代表了对人类心血管系统调节至关重要的不同大小的交感神经元的放电。为了实现这一长期目标，我的研究计划提出了四个短期目标：1)通过探索调节这种以前被忽视的放电模式的机制，扩大我们最近发现的一种异步放电（爆发之间）的交感神经ap亚群的新发现；2)基于我们最近的发现，通过应用一种新技术，动脉压力反射对交感神经AP亚群的差异调节，揭示了压力反射调节的全部复杂性；3)发现脑和中枢神经系统肾上腺素能神经元对交感AP亚群放电模式的贡献；4)探讨生理性别对交感神经AP亚群的释放和招募模式的影响。意义和影响：我的创新研究项目将通过了解不同大小的交感神经元传递到血管的AP信息，推进我们对交感神经系统如何传达心血管调节的认识。这项研究将推动我所在领域的方法转变，从依赖简化的综合交感神经记录到高质量的微神经记录，从而能够研究不同大小的交感神经元的AP放电模式。该研究计划将为高素质的人员提供学习世界上少数实验室所采用的尖端技术的机会。总的来说，这项研究有助于我们对人类大脑和神经系统如何确保最佳生物功能（如血压稳态）的永久好奇。

My long-term vision is to generate knowledge regarding sympathetic regulation of the cardiovascular system in humans. To keep humans alive during physiological stressors such as physical exercise or standing upright, the sympathetic nervous system communicates cardiovascular adjustments that ensure optimal blood pressure and blood flow. To do this, the sympathetic nervous system relies on differently sized neurons that deliver to the circulation precise neural messages known as action potentials (APs). Using microneurography to study sympathetic AP firing patterns in humans, we have learned the basic neuronal firing and recruitment strategies the sympathetic nervous system uses to communicate cardiovascular adjustments. However, new discoveries have challenged our fundamental understanding of both sympathetic AP firing patterns and the mechanisms regulating these firing patterns, highlighting that our knowledge of sympathetic AP discharge remains in its infancy. Thus, the long-term objective of my research program is to advance our understanding of sympathetic AP subpopulation discharge, which represents the firing of differently sized sympathetic neurons that are critical for the regulation of the human cardiovascular system. To achieve this long-term objective, my research program proposes four short-term objectives: 1) Expand our recent novel discovery of a subpopulation of sympathetic APs that fires asynchronously (between-bursts) by probing the mechanisms regulating this previously overlooked discharge pattern; 2) Build on our recent discovery that the arterial baroreflex differentially regulates sympathetic AP subpopulations by applying a new technique that exposes the full complexity of baroreflex regulation; 3) Discover the contribution of adrenergic neurons in the brain and central nervous system to the discharge pattern of sympathetic AP subpopulations; 4) Explore the impact of biological sex on discharge and recruitment patterns of sympathetic AP subpopulations. Significance and Impact: My innovative research program will advance our knowledge of how the sympathetic nervous system communicates cardiovascular adjustments by learning about the AP messages delivered to the blood vessels by differently sized sympathetic neurons. This research will drive forward the methodological shift in my field from the reliance on simplified integrated sympathetic recordings to high-quality microneurographic recordings that enable the study of AP firing patterns of differently sized sympathetic neurons. This research program will provide highly qualified personnel with the opportunity to learn cutting-edge techniques performed by few laboratories worldwide. Overall, this research contributes to our perpetual curiosity of how the human brain and nervous systems ensure optimal biological functions, such as blood pressure homeostasis.