BLOOD PRESSURE CONTROL BY FOREBRAIN & BRAINSTEM NEURONS

描述（申请人提供）：该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设，1）影响基底交感神经放电（SND）和膈神经活动（PNA）反映的呼吸节律，2）介导SND，血压（BP），以及由迷走神经和交感神经传入神经的阵列的激活产生的呼吸。这些项目建立在当前资助期间完成的工作基础上，通过关注延髓外侧被盖区（LTF）中经常被忽视的“经典加压区”，从独特的角度解决问题。在项目#1中描述的实验是第一个试图识别对LTF交感兴奋性神经元的兴奋性驱动源的实验，其有助于设定SND的基础水平。这些实验对静息血压的神经源性支持产生的机制有重要意义。项目#2和3提供了对不同类型内脏受体（机械受体、化学敏感受体）的“自然”激活可以改变传出SND、PNA并最终改变心肺功能的机制的首次全面评估。反射涉及来自心肺、胃肠和肾受体的有髓和无髓纤维的激活，并且反应包括SND和/或PNA的激发和抑制。这些反射被认为有助于在生理（例如，肺膨胀、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管功能障碍）。项目#4解决了LTF在确定中心呼吸频率方面先前未被认识到的作用。这些研究预计将表明，髓回路调节SND更复杂的组织比在大多数目前的审查和LTF在调节呼吸节律中发挥了迄今为止尚未认识到的作用。

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.