Spinal hierachy and noxious cardiac sensory processing

描述（由申请人提供）：本项目旨在评估与心脏相关的迷走神经和交感感觉输入如何影响上颈（C1-C2）和上胸（T3-T4）脊髓神经元，最终改变向心脏输出的输出神经元。这一建议是基于最近的观察，C1-C2神经元调节腰骶神经元对骨盆输入的反应，迷走感觉信息激发C1-C2神经元，心脏交感神经输入到胸椎段通过本体脊髓通路上升，影响C1-C2神经元。我们假设，在调节心功能的神经控制层次中，C1-C2脊髓的神经元影响胸上神经元对心脏感觉信息的处理，从而决定流向心脏的自主神经流出。神经生理学实验旨在确定C1-C2和T3-T4神经元对化学或缺血性心脏应激产生的迷走神经和交感传入输入的加工，并确定上颈神经元加工对T3-T4神经元的影响。神经解剖学实验（测量c-Fos表达和从上颈节段追踪本体脊髓通路）旨在确定心脏应激时神经元的激活，并为本体脊髓解剖组织提供证据。每个特定目的的微透析实验将测量在基础状态和心脏应激时心室心肌间质液中的去甲肾上腺素和肾上腺素水平。心包内注射致痛化学物质或冠状动脉闭塞会产生心脏应激。具体目的是研究1)在双侧迷走神经切断术前后和激活T3-T4段GABAB受体前后，C1-C2下行本体脊髓神经元的心脏感觉加工和C1-C2和T3-T4段c-Fos的表达；2)破坏或刺激C1-C2节段细胞体对T3-T4神经元的影响及c-Fos表达的测定；3)急性心肌缺血的影响；4)短期脊髓背激活对心脏信息加工的影响。这些研究将为确定C1-C2神经元对心脏控制层次的影响提供基础。

DESCRIPTION (provided by applicant): 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.