The purpose of this project is to evaluate how cardiac-related vagal and sympathetic sensory inputs influence upper cervical (C1-C2) and upper thoracic (T3-T4) spinal neurons to ultimately modify efferent neuronal output to the heart. This proposal is based on recent observations that C1-C2 neurons modulate responses of lumbosacral neurons to pelvic inputs, that vagal sensory information excites C1-C2 neurons, and that cardiac sympathetic input to thoracic segments ascends via propriospinal pathways to influence C1-C2 neurons. We hypothesize that, within the hierarchy of neural control that regulates cardiac function, neurons in C1-C2 spinal cord influence the processing of cardiac sensory information in upper thoracic neurons, and thereby determine autonomic outflow to the heart. Neurophysiological experiments are designed to determine the processing of vagal and sympathetic afferent inputs produced by chemical or ischemic cardiac stress in C1-C2 and T3-T4 neurons, and to determine the influence of upper cervical neuronal processing on T3-T4 neurons. Neuroanatomical experiments (measurement of c-Fos expression and tract tracing of propriospinal pathways from upper cervical segments) are designed to determine neuronal activation during cardiac stress and to provide evidence for propriospinal anatomical organization. Microdialysis experiments in each specific aim will measure norepinephrine and epinephrine levels in the interstitial fluid of the ventricular myocardium in the basal state and during cardiac stress. Cardiac stress will be produced by intrapericardial injection of algogenic chemicals or by coronary artery occlusion. Specific aims will address 1) cardiac sensory processing in C1-C2 descending propriospinal neurons and c-Fos expression in C1-C2 and T3-T4 segments before and after bilateral vagotomy and before and after activating GABAB receptors in T3-T4 segments; 2) effects of disrupting or stimulating cell bodies in C1-C2 segments on T3-T4 neurons, and measurements of c-Fos expression; 3) effects of acute myocardial ischemia; 4) effects of short-term dorsal cord activation on cardiac information processing. These studies will provide a basis for determining the impact of C1-C2 neurons on the hierarchy of cardiac control.

R01HL075524

2004-05-15

2009-04-30