BLOOD PRESSURE CONTROL BY FOREBRAIN & BRAINSTEM NEURONS

描述（由申请人提供）：该研究计划分为四个紧密相连的项目，将测试有关中枢神经回路的新假设：1)影响基底交感神经放电（SND）和由膈神经活动（PNA）反映的呼吸节律；2)通过激活一系列迷走神经和交感传入神经介导基底交感神经放电（SND）、血压（BP）和呼吸的变化。这些项目以当前资助期内完成的工作为基础，从一个独特的角度解决问题，重点关注髓质外侧被盖区（LTF）中经常被忽视的“经典压力区”。项目1中描述的实验是第一个试图确定ltf交感神经兴奋性驱动的来源，帮助设定SND的基础水平。这些实验对静息血压神经源性支持的产生机制具有重要意义。项目#2和3首次全面评估了不同类型的内脏受体（机械受体，化学敏感受体）的“自然”激活可以改变输出SND， PNA并最终改变心肺功能的机制。反射包括来自心肺、胃肠道和肾脏受体的有髓和无髓纤维的激活，反应包括SND和/或PNA的兴奋和抑制。这些反射被认为有助于在生理（如肺膨胀、消化、液体平衡）和病理生理状态（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）中注意到的心肺变化。项目#4解决了以前未被认识到的LTF在决定中枢呼吸速率方面的作用。这些研究有望表明调节SND的髓质回路比目前大多数综述所描述的组织更复杂，并且LTF在调节呼吸节律中起着迄今未被认识的作用。

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.