Central Interaction of Baroreceptor & Somatic Afferents

压力感受器的中枢相互作用

基本信息

批准号：
7559864
负责人：
Jeffrey Thomas Potts
金额：
$ 17.07万
依托单位：
UNIVERSITY OF NORTH TEXAS HLTH SCI CTR
依托单位国家：
美国
项目类别：
财政年份：
1999
资助国家：
美国
起止时间：
1999-04-01 至 2009-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7559864
关键词：
Agonist Aminobutyric Acid Aminobutyric Acids Anesthesia procedures Animals Award Baroreflex Brain Brain Stem Cardiovascular Physiology Cardiovascular system Cell Nucleus Data Disease Exercise Feedback Fiber GABA Receptor Heart Heart failure Homeostasis Hypertension In Situ Knowledge Mediating Microelectrodes Microinjections Motor Motor Activity Neurons Nociception Nucleus solitarius Pain Pathway interactions Physiological Preparation Pressoreceptors Process Rattus Reflex action Reporting Research Personnel Role Sensory Sensory Process Signal Transduction Skeletal Muscle Spinal Stress Substance P Substance P Receptor Synapses Synaptic Transmission Testing Work base blood pressure regulation expectation gamma-Aminobutyric Acid human study in vivo innovation neural circuit programs receptor relating to nervous system response sensory feedback sensory stimulus somatosensory young adult

项目摘要

DESCRIPTION (provided by applicant): Exercise alters arterial baroreceptor reflex function. However, the central mechanisms that modulate the arterial baroreflex during exercise are not completely understood. Arterial baroreceptor and skeletal muscle receptor afferents are stimulated during exercise and transmit sensory information to the nucleus tractus solitarii (NTS). The NTS is the major sensory nucleus in the mammalian brainstem that processes and relays these inputs to other medullary and supra-medullary nuclei controlling autonomic motor outflow. Previous work during the initial tenure of this award, along with preliminary data for this competitive renewal, has demonstrated that synaptic input from skeletal muscle receptors inhibits arterial baroreceptor signaling by activating local GABAergic and SPergic circuits in the NTS. The specific aims for this application are: 1) to determine the role GABAergic and SPergic mechanisms on central baroreflex control of vagal and sympathetic motor activity; 2) to characterize the synaptic responses of functionally-identified single-unit NTS neurons and to determine the contribution of GABAergic and SPergic receptors on neuronal and network excitability; and 3) to determine the role of innocuous and noxious feedback from skeletal muscle on arterial baroreflex function. To accomplish these aims, physiological paradigms will be used to activate arterial baroreceptors and contraction-sensitive / nociceptive skeletal muscle receptors using an in situ unanesthetized, arterially perfused working heart-brainstem preparation and an in vivo unanesthetized decerebrate preparation in young adult rats. The role of GABAergic and SPergic mechanisms in the NTS will be examined by central microinjections of selective agonists and antagonists for GABA receptors and neurokinin-1 receptors, as well as picoejection of these compounds directly onto functionally identified single-unit NTS neurons using multibarrel microelectrodes. Results from these studies will provide new information regarding the role of NTS neurons in the sensory processing of neural feedback from arterial baroreceptors and skeletal muscle receptors. This knowledge will extend our understanding of the central interaction between baroreceptor and somatic afferents at the level of the NTS and will provide a cellular basis to explain the synaptic mechanisms underlying baroreflex resetting during exercise.

描述（由申请人提供）：运动改变动脉压力感受器反射功能。然而，运动过程中调节动脉压力反射的中心机制尚不完全清楚。运动期间，动脉压力感受器和骨骼肌感受器传入受到刺激，并将感觉信息传输至孤束核 (NTS)。 NTS 是哺乳动物脑干中的主要感觉核，负责处理这些输入并将这些输入传递到其他控制自主运动输出的髓质和髓上核。该奖项最初任职期间的先前工作以及本次竞争性更新的初步数据表明，骨骼肌受体的突触输入通过激活 NTS 中的局部 GABA 能和 SPergic 回路来抑制动脉压力感受器信号传导。该应用的具体目标是：1) 确定 GABAergic 和 SPergic 机制对迷走神经和交感神经运动活动的中枢压力反射控制的作用； 2) 表征功能鉴定的单单元 NTS 神经元的突触反应，并确定 GABAergic 和 SPergic 受体对神经元和网络兴奋性的贡献； 3) 确定骨骼肌无害和有害反馈对动脉压力反射功能的作用。为了实现这些目标，生理学范式将用于在年轻成年大鼠中使用原位未麻醉、动脉灌注工作心脑干制剂和体内未麻醉去脑制剂来激活动脉压力感受器和收缩敏感/伤害性骨骼肌受体。 GABAergic 和 SPergic 机制在 NTS 中的作用将通过中央显微注射 GABA 受体和神经激肽-1 受体的选择性激动剂和拮抗剂，以及使用多管微电极将这些化合物直接皮喷射到功能上识别的单单元 NTS 神经元上来检查。这些研究的结果将提供有关 NTS 神经元在动脉压力感受器和骨骼肌受体的神经反馈感觉处理中的作用的新信息。这些知识将扩展我们对 NTS 水平上压力感受器和躯体传入神经之间的中心相互作用的理解，并将为解释运动期间压力感受反射重置的突触机制提供细胞基础。