Exploring sympathetic neuronal discharge patterns communicating homeostatic cardiovascular adjustments in humans

我的长期愿景是产生关于人类心血管系统交感神经调节的知识。为了在身体锻炼或直立站立等生理压力下保持人类的生存，交感神经系统与心血管调节进行沟通，以确保最佳的血压和血液流动。要做到这一点，交感神经系统依赖于不同大小的神经元，这些神经元向血液循环传递被称为动作电位(AP)的精确神经信息。使用显微神经学研究人类交感神经AP的放电模式，我们已经了解了交感神经系统用来传递心血管调节的基本神经元放电和招募策略。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，突显了我们对交感AP放电的了解仍处于初级阶段。因此，我的研究计划的长期目标是促进我们对交感AP亚群放电的理解，交感AP亚群放电代表着对人类心血管系统的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)通过探索调节这一以前被忽视的放电模式的机制，扩大我们最近发现的交感AP亚群的异步(阵发之间)放电；2)基于我们最近发现的动脉压力感受性反射对交感AP亚群的差异性调节，应用一种揭示压力反射调节全部复杂性的新技术；3)发现大脑和中枢神经系统中的肾上腺素能神经元对交感AP亚群的放电模式的贡献；4)探索生物性别对交感AP亚群的放电和招募模式的影响。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向血管传递的AP信息，来促进我们对交感神经系统如何传达心血管调节的了解。这项研究将推动我所在领域的方法论转变，从依赖简化的综合交感神经记录到高质量的显微神经学记录，从而能够研究不同大小交感神经元的AP放电模式。这一研究计划将为高素质的人员提供学习世界上少数几个实验室进行的尖端技术的机会。总体而言，这项研究有助于我们永远好奇人类的大脑和神经系统如何确保最佳的生物功能，如血压动态平衡。

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.