Neural Substrates of EA in Cardiovascular Control

描述（由申请人提供）：针灸是一种古老的治疗方式，其作用机制直到最近才被定义。虽然临床试验正在确定在疼痛、感染和心血管疾病（包括高血压、心肌缺血和心律失常）等领域的疗效，但很明显，我们对其作用机制知之甚少。在过去的三年里，该基金探索了长环路通路的功能，包括下丘脑腹侧弓状核（ARC）、中脑腹侧导水管周围灰质（vIPAG）和延髓吻侧腹侧（rVLM）在内脏交感兴奋性反射的调节中。我们已经证明，电针（EA）激活时，位于远端正中神经和腓深体神经沿线的穴位对ARC、vIPAG和rVLM的兴奋性输入。ARC向vIPAG提供兴奋性投射，vIPAG反过来向rVLM提供抑制性投射，rVLM最终调节交感前运动神经元，交感前运动神经元支配脊髓交感神经流向心血管系统。目前的赠款改进和扩展了我们以前的观察，有三个具体目标。第一个目的是评估ARC和vIPAG之间相互投射的重要性，我们假设，这加强了EA期间体细胞传入刺激对ARC的输入。第二个目的是确定特定神经递质系统的作用，包括ARC和vIPAG中的谷氨酸及其嗜离子受体，ARC中的乙酰胆碱和vIPAG中的内源性大麻素系统，我们假设。抑制γ -氨基丁酸的释放，解除对vIPAG神经元活性的抑制，最终增强vIPAG对rVLM的抑制作用。第三个目的是研究中线髓核的作用，特别是中缝暗核、大核和苍白球核，我们认为这些核接受来自vIPAG的兴奋输入，进而抑制rVLM的活性。研究将结合解剖学、细胞电生理学、药理学、微收集-微测定和全动物反射方法来检验这些假设。这些增加的知识将使医生和科学家对EA对心血管影响的机理有更深入的了解，这将增加其临床接受度，例如心血管疾病患者。此外，针灸的机制基础知识可以使从业人员优化临床心血管治疗反应。

DESCRIPTION (provided by applicant): Acupuncture is an ancient therapeutic modality whose mechanisms of action only recently are being defined. While clinical trials are defining efficacy in areas such as pain, infections and cardiovascular disease, including hypertension, myocardial ischemia and arrhythmias, it is clear that we know little about its mechanisms of action. Over the last three year, this grant has explored the function of a long-loop pathway, including the arcuate nucleus (ARC) in the ventral hypothalamus, the ventrolateral periaqueductal gray (vIPAG) in the midbrain and the rostral ventrolateral medulla (rVLM) in regulation of visceral sympathoexcitatory reflexes. We have demonstrated excitatory input from acupuncture points located along the distal median and deep peroneal somatic nerves activated during electroacupuncture (EA) to the ARC, vIPAG and rVLM. The ARC provides an excitatory projection to the vIPAG, which in turn, provides an inhibitory projection to the rVLM that ultimately regulates sympathetic premotor neurons that innervate the spinal cord sympathetic outflow to the cardiovascular system. The present grant refines and extends our previous observations with three specific aims. The first aim evaluates the significance of reciprocal projections between the ARC and the vIPAG, which we hypothesize, reinforces input in the ARC from somatic afferent stimulation during EA. The second aim identifies the role of specific neurotransmitter systems, including glutamate and its ionotropic receptors in ARC and vIPAG, acetylcholine in ARC and the endocannabinoid system in vIPAG, which we hypothesize, inhibits the release of gamma-aminobutyric acid to disinhibit vIPAG neuronal activity and ultimately potentiate vIPAG inhibition of the rVLM. The third aim examines the role of midline medullary nuclei, especially the nuclei raphe obscurus, magnus and pallidus, which we believe receive excitatory input from the vIPAG and, in turn, inhibit rVLM activity. Studies will use a combination of anatomical, cellular electrophysiological, pharmacological, microcollection-microassay and whole animal reflex approaches to test these hypotheses. This added knowledge will provide physicians and scientists with a greater mechanistic understanding of EA's cardiovascular influence, which will increase its clinical acceptance, e.g., in patients with cardiovascular disease. Furthermore, knowledge of the mechanistic basis of acupuncture may allow practitioners to optimize the clinical cardiovascular responses to treatment.