Grant: Discovery Grants Program - Individual

Research Program Objective: Understand the neurological communication strategies used by the sympathetic nervous system (SNS) to control blood pressure and regulate the distribution of blood flow in the face of physiological stress. We are testing the working hypothesis that the SNS expresses a complex but deterministic language expressed in its recruitment of various families of neurons as well as modifications of the timing of the neuronal firing patterns. Background: Survival depends upon rapid and accurate communication of external and internal stressors to vital internal organs, leading to functional changes to deal with the stress. For example, corrective action taken to keep blood pressure from falling when you stand up requires an intricate linkage between neural sensors in your body that inform the brain about the problem which then modifies the outflow of sympathetic nerve activity (SNA) to adjust the function of heart and blood vessels to protect blood pressure. In general, neural systems rely on patterns of neural firing to communicate precisely the details of the stimulus. However, our understanding of the neural “language” used by the SNS to communicate and correct stress-induced physiological disturbances remains very superficial. Using direct neural recordings in humans, we have characterized complex SNS recruitment strategies, including i) modifications of firing rate of axons already recruited at baseline, ii) recruitment of additional neural populations during stress, and iii) variations in the timing of these axonal firing patterns. We now aim to improve our understanding of the mechanisms controlling these neural recruitment patterns as well as their interpretation by blood vessels as measured in their patterns of vasoconstriction. Research Aims: 1) Determine the brain regions and possible neural control mechanisms associated with the specific SNA patterns, 2) Develop methods that manipulate these communication patterns in a titrated manner to study further the interactions between sensory and sympathetic neural systems, and 3) Quantify how SNA signals are interpreted by blood vessels in terms of the magnitude of vasoconstriction. Using a variety of physiological stressors, we will assess relationships between SNA action potential recruitment (microneurography), functional brain activation (neuroimaging), and muscle blood flow (ultrasound and diffusive correlative spectroscopy). These studies are highly novel and address a fundamental homeostatic principle that enhances animal survival through acute and chronic adaptations to stress.