Spinal hierarchy and noxious cardiac sensory processing

描述(申请人提供)：这个项目的目的是评估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，最终改变到心脏的传出神经元输出。这一建议是基于最近的观察结果，即C1-C2神经元调节腰骶神经元对盆腔输入的反应，迷走神经感觉信息兴奋C1-C2神经元，心脏交感神经传入胸段通过固有脊髓通路影响C1-C2神经元。我们假设，在调节心脏功能的神经控制层次中，C1-C2脊髓中的神经元影响上胸神经元对心脏感觉信息的处理，从而决定自主神经流出到心脏。神经生理学实验旨在确定化学应激或缺血性心脏应激在C1-C2和T3-T4神经元中产生的迷走神经和交感传入信息的加工过程，并确定上颈区神经元加工对T3-T4神经元的影响。神经解剖学实验(c-Fos表达的测量和上颈段固有脊髓通路的追踪)旨在确定心脏应激时神经元的激活，并为固有脊髓的解剖组织提供证据。每个特定目标的微透析实验将测量基础状态和心脏应激期间心室肌间质液中去甲肾上腺素和肾上腺素的水平。心脏应激可通过心包内注射致过敏物质或冠状动脉闭塞来产生。具体目标将涉及：1)双侧迷走神经切断术前后，激活T3-T4节段GABAB受体前后，C1-C2下行固有脊髓神经元的心脏感觉加工及c-Fos表达；2)干扰或刺激C1-C2节段胞体，及c-Fos表达的影响；3)急性心肌缺血的影响；4)短期脊髓背索激活对心脏信息处理的影响。这些研究将为确定C1-C2神经元对心脏控制等级的影响提供基础。

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.