CHEMORECEPTOR INPUT TO NONRESPIRATORY CELLS IN NTS

NTS 中非呼吸细胞的化学受体输入

• 批准号: 2220185
• 负责人: Steven W Mifflin
• 金额: $ 19.35万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-04-01 至 1998-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2220185
• 关键词: NMDA receptors; afferent nerve; axon; baroreceptors; carotid sinus; chemoreceptors; electron microscopy; electrostimulus; evoked potentials; excitatory aminoacid; glutamates; inhibitor /antagonist; laboratory rat; neural transmission; neuroanatomy; neuropeptide receptor; neurotransmitter receptor; receptor expression; solitary tract nucleus; substance P; synapses; tachykinin

This proposal represents a continuing effort to identify the cellular mechanisms which underlie the integration of peripheral, cardio- respiratory afferent inputs within the central nervous system. I will continue to investigate the integration of arterial chemoreceptor (CR) afferent inputs within the nucleus tractus solitarius (NTS), the initial site of termination of CR afferent fibers within the central nervous system. During the previous funding period the synaptic basis of CR afferent integration within NTS was examined. This proposal will extend these observations and begin an examination of the pharmacological mechanisms which underlie CR afferent integration within the NTS. Specifically, the role of two neurotransmitter receptors which have been implicated as possible mediators of CR evoked excitation of NTS neurons will be examined. A large body of evidence suggests that both excitatory amino acid and tachykinin receptors within NTS play a role in chemoreflex regulation of the cardiovascular and respiratory systems. This proposal will use two complimentary approaches to investigate the possible role of excitatory amino acid and tachykinin receptors in the integration of CR inputs within NTS in anesthetized rats. Extracellular recording and iontophoretic techniques will be used to examine NTS neurons receiving mono- and/or poly-synaptic CR inputs and determine the effects of excitatory amino acid and tachykinin receptor agonists and antagonists on (1) spontaneous discharge, (2) carotid sinus nerve evoked discharge and (3) CR evoked discharge. Intracellular recording techniques will be used to further study the integration of CR afferent inputs within NTS by examining (1) membrane potential responses to a graded series of CR stimuli and (2) if the response to activation of CR inputs is altered (enhanced) during and following high frequency stimulation of the carotid sinus nerve. Intracellular recording techniques will be used in combination with immunohistochemical techniques to determine morphology, axonal projection, and the anatomical relationships between tachykinin (Substance P) immunoreactive elements and NTS neurons receiving CR inputs at both the light and electron microscopic level. The immunohistochemical studies will provide insights into the anatomical substrates of afferent integration within NTS, while the iontophoretic studies will provide insights into the functional significance of neuroactive substances previously implicated in cardio-respiratory regulation. These studies will extend our understanding of physiological and pharmacological mechanisms mediating the central integration of CR afferent inputs. Such information is critical if we are to fully understand mechanisms by which the central nervous system regulates blood pressure and respiration in normal (e.g., exercise, sleep) and pathophysiological conditions (e.g., hypertension, hypoxia and hemorrhage).

该提案代表了识别细胞的持续努力 基于周围，心脏 - 中枢神经系统内的呼吸传入输入。我会 继续研究动脉化学感受器（CR）的整合 原子核Solitarius（NTS）中的传入输入，初始 中枢神经内CR传入纤维的终止部位 系统。在上一个资金期间，CR的突触基础 检查了NTS中的传入集成。该提议将延长 这些观察结果并开始检查药理学 NTS内CR的基础的机制。 具体而言，两个神经递质受体的作用 与Cr诱发的NTS神经元激发的介导者有关 将被检查。大量证据表明两者都兴奋 NTS中的氨基酸和速素受体在化学反射中起作用 心血管和呼吸系统的调节。这个建议 将使用两种免费方法来研究可能的作用 兴奋性氨基酸和速气素受体 麻醉大鼠NTS内的CR输入。细胞外记录和 离子遗传学技术将用于检查接收的NTS神经元 单突触CR输入，并确定 兴奋性氨基酸和速气蛋白受体激动剂和拮抗剂 在（1）自发放电，（2）颈动脉窦神经诱发的排放 （3）CR引起的排放。细胞内记录技术将是 用于进一步研究NTS中CR传入输入的整合 通过检查（1）对一系列CR的膜电位响应 刺激和（2）如果改变了Cr输入激活的响应 （增强）在颈动脉的高频刺激期间和之后 窦神经。细胞内记录技术将用于 结合免疫组织化学技术来确定形态， 轴突投射和速素之间的解剖学关系 （物质P）接收CR输入的免疫反应元件和NTS神经元 在光和电子显微镜水平上。免疫组织化学 研究将提供有关传入的解剖基板的见解 在NTS中的整合，而离子遗漏研究将提供 洞悉神经活性物质的功能意义 以前与心脏呼吸器调节有关。这些研究 将扩展我们对生理和药理的理解 介导CR传入输入的中心整合的机制。这样的 如果我们要充分了解该机制，那么信息至关重要 中枢神经系统调节血压和呼吸 正常（例如运动，睡眠）和病理生理状况（例如， 高血压，缺氧和出血）。