Exploring sympathetic neuronal discharge patterns communicating homeostatic cardiovascular adjustments in humans

探索交流人类稳态心血管调节的交感神经元放电模式

• 批准号: RGPIN-2022-05293
• 负责人: Klassen, Stephen
• 金额: $ 2.11万
• 依托单位: Brock University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2022
• 资助国家: 加拿大
• 起止时间: 2022-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=757745
• 关键词: Exploring; sympathetic; neuronal; discharge; patterns

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.

我的长期愿景是获得有关人类心血管系统交感神经调节的知识。为了使人类在生理压力（如体育锻炼或直立）期间保持活力，交感神经系统传达心血管调节，以确保最佳血压和血流。为了做到这一点，交感神经系统依赖于不同大小的神经元，这些神经元向循环传递称为动作电位（AP）的精确神经信息。使用显微神经摄影术研究人类交感神经AP放电模式，我们已经了解了交感神经系统用于传达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神经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神经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促进我们对交感神经AP亚群放电的理解，这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）扩展我们最近发现的一个异步激发交感神经AP亚群通过探测调节这种以前被忽视的放电模式的机制;（二）基于我们最近发现的动脉压力感受器反射差异调节交感神经AP亚群，通过应用一种新技术，本文的主要工作包括：（1）探讨压力感受性反射调节的复杂性;（2）探讨脑和中枢神经系统中肾上腺素能神经元对交感神经AP亚群放电模式的贡献;（3）探讨生物性别对交感神经AP亚群放电和募集模式的影响。意义和影响：我的创新研究计划将通过学习不同大小的交感神经元传递给血管的AP信息来推进我们对交感神经系统如何传达心血管调节的知识。这项研究将推动我的领域的方法转变，从依赖简化的综合交感神经记录到高质量的显微神经记录，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各地少数实验室所执行的尖端技术的机会。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）的永久好奇心。