Grant: Discovery Grants Program - Individual

Understanding sympathetic discharge patterns, their modulation? and their cardiovascular impact, forms a major program of research in our laboratory. Through the sympathetic nervous system the brain emits bursts of neural activity that vary in frequency and the number of neurons making up the bursts. Our recent research exposed the various action potentials making up each burst and the existence of subpopulations that vary in conduction speed and recruitment patterns. Specifically, there exists a group of large and fast-conducting axons that are reserved for high-stress scenarios. What brain structures, and mechanisms regulate recruitment of these AP groups? A potent determinant of sympathetic outflow lies in the baroreceptors that sense blood pressure. The aims of the present research are to determine: 1) how sensory nerves from baroreceptors in the carotid sinus (neck) affect AP recruitment, 2) what brain structures are involved in the baroreflex control of AP recruitment, 3) the role of the paraspinal ganglia in this recruitment process, and 4) how a relatively common genetic variation (approximately 7% of Caucasians) in adenylate cyclase affects AP recruitment through augmented cardiac function and baroreceptor activation. The current research will combine existing microneurographic analysis of AP recruitment and functional neuroimaging of brain activation patterns, during manipulations of baroreceptor inputs and pharmacological manipulations of neurotransmission through the sympathetic synaptic pathways, to study the neurophysiologic basis of AP recruitment. This work will produce new knowledge regarding baroreflex-mediated AP recruitment and the impact of relevant modifiers of sympathetic outflow. In addition, the research will develop new technologies that enable baroreflex stimuli to be studied experimentally in the magnetic resonance imaging environment. Finally, the research will contribute to the long-standing need for information regarding the brain's involvement in blood pressure control with new techniques and technology to expose such mechanisms.