Grant: Discovery Grants Program - Individual

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.