BLOOD PRESSURE CONTROL BY FOREBRAIN & BRAINSTEM NEURONS

描述(申请人提供)：研究计划分为四个紧密相连的项目，将测试关于中枢神经回路的新假说，1)影响基础交感神经放电(SND)和由膈神经活动(PNA)反映的呼吸节律，2)调节由迷走神经和交感传入神经激活产生的SND、血压和呼吸的变化。这些项目建立在当前供资期间完成的工作的基础上，并从独特的角度解决问题，重点放在延髓外侧被盖区(LTF)中经常被忽视的“经典升压区”。项目1中描述的实验是第一次试图确定LTF交感兴奋神经元的兴奋性驱动的来源(S)，这有助于设定SND的基础水平。这些实验对静息BP产生神经源性支持的机制有重大影响。项目2和3首次对不同类型的内脏感受器(机械感受器、化学敏感性感受器)的“自然”激活可以改变传出SND、PNA以及最终心肺功能的机制进行了全面评估。这些反射包括激活心肺、胃肠和肾脏受体的有髓和无髓纤维，反应包括兴奋和抑制SND和/或PNA。这些反射被认为有助于在生理状态(例如肺充气、消化、液体平衡)以及病理生理状态(例如充血性心力衰竭、心肌缺血、婴儿猝死综合征和食道功能障碍)时注意到的心肺变化。项目4解决了LTF在确定中心呼吸频率方面以前未被认识到的作用。这些研究有望表明，调节SND的延髓回路比目前大多数综述中描述的更复杂，LTF在调节呼吸节律方面发挥着迄今未被认识到的作用。

DESCRIPTION (provided by applicant): The Research Plan is divided into four tightly inter-linked projects that will test novel hypotheses regarding the central neural circuitry that 1) affects basal sympathetic nerve discharge (SND) and the respiratory rhythm as reflected by phrenic nerve activity (PNA) and 2) mediates changes in SND, blood pressure (BP), and respiration produced by activation of an array of vagal and sympathetic afferents. These projects build on work completed during the current funding period and address problems from a unique perspective by focusing on the often ignored "classic pressor area" in the medullary lateral tegmental field (LTF). The experiments described in Project #1 are the first to seek to identify the source(s) of excitatory drive to LTFsympathoexcitatory neurons that help set the basal level of SND. These experiments have significant bearing on the mechanism by which the neurogenic support for resting BP is generated. Projects #2 & 3 provide the first comprehensive assessment of mechanisms by which "natural" activation of different types of visceral receptors (mechanoreceptors, chemosensitive receptors) can alter efferent SND, PNA, and ultimately cardiorespiratory function. The reflexes involve activation of myelinated and unmyelinated fibers from cardiopulmonary, gastrointestinal, and renal receptors, and responses include both excitation and inhibition of SND and/or PNA. These reflexes are thought to contribute to cardiorespiratory changes noted during physiological (e.g., lung inflation, digestion, fluid balance) as well as pathophysiological states (e.g., congestive heart failure, myocardial ischemia, sudden infant death syndrome, and esophageal dysfunction). Project #4 addresses the previously unrecognized role of the LTF in determining central respiratory rate. These studies are expected to show that medullary circuits regulating SND are more complexly organized than depicted in most current reviews and that the LTF plays a hitherto unrecognized role in regulating the respiratory rhythm.