Grant: Discovery Grants Program - Individual

Animal survival depends upon the ability to adapt rapidly to stress. This adaptation is accomplished through changes in a system of nerves, called the autonomic nervous system. These nerve signals emerge from the brain to regulate heart function and blood vessels, which in turn, helps control blood pressure. Despite over a century of research analyzing this "brain-heart axis" in humans, much remains to be understood regarding the fundamentals of how the brain's neural signals are encoded by the brain and decoded by the heart or blood vessels. Following recent progress, the proposed research will study how the brain's autonomic network is involved in the control of heart function and blood vessels. The nerve signals from a nerve in the lower leg are recorded as action potentials (AP) which represent electrical discharges of individual neurons that can be studied individually or as groups of synchronized APs in what is called a "burst". The approach we developed to detect and organize AP patterns is gaining in popularity. However, its use is limited by the specific tools required to collect this nerve activity. Therefore, Objective 1 will provide an improved open-access nerve AP detection technology. While the regions of the brain involved in cardiovascular control are understood, the way they work together as a network is not understood. Neither is it understood how this network integrates nerve signals coming into the brain with the autonomic signals sent out of the brain. Therefore, Objective 2 will develop approaches to electrically stimulate sensory nerves arising from muscle and the outer ear and determine how they affect the brain's autonomic network, heart function, AP patterns and vascular function. Further, we have exposed the complex nature of AP discharge patterns and their recruitment but how these features are interpreted by the blood vessels remains poorly understood. Objective 3 will discover how the AP patterns are decoded by the smallest blood vessels using advanced laser imaging technology. Finally, discovering important relationships in the neural system that affects cardiovascular control is challenged by inter-individual variations among the brain, neural and cardiovascular responses. To improve our ability to interpret this brain-heart axis, we will explore indicators in blood, lifetime behaviours, and sex-specific determinants of neuro-cardiovascular outcomes. These studies will increase our fundamental understanding of neural control in the circulatory system, with implications for understanding inter-organ communications that accommodate normal stressors. The research engages multiple disciplines including physiology, mathematics, and medical biophysics and will create unique multidisciplinary training opportunities for undergraduate, graduate and post-graduate trainees, as well as lead to the development of new methodologies that manipulate, quantify and, thereby, understand, neural control of cardiovascular function.