Presynaptic Mechanisms of Neurotransmission in NTS

NTS 中神经传递的突触前机制

• 批准号: 7337370
• 负责人: Michael Christian Andresen
• 金额: $ 34.75万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-01-01 至 2009-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7337370
• 关键词: Address; Afferent Neurons; Automobile Driving; Axon; Baroreflex; Brain Stem; Calcium; Calcium Channel; Cardiovascular system; Cephalic; Characteristics; Chromosome Pairing; Class; Cranial Nerves; Disease; Electrophysiology (science); Exocytosis; Fluorescent Dyes; Foundations; Frequencies; Glutamates; Heart failure; Homeostasis; Hypertension; Image; In Vitro; Individual; Intensive Care; Investigation; Ion Channel; Knowledge; Label; Laboratories; Life; Link; Methods; Molecular; Morphology; N-Type Calcium Channels; Nerve; Neuromodulator; Neurons; Nucleus solitarius; Opioid Receptor; Optics; Output; Pathogenesis; Pathway interactions; Peptides; Peripheral; Pharmaceutical Preparations; Physicians; Potassium; Potassium Channel; Preparation; Pressoreceptors; Presynaptic Terminals; Property; Prosencephalon; Range; Records; Reflex action; Regulation; Research; Research Personnel; Respiratory System; Role; Scientist; Shock; Sodium; Stroke; Structure; Synapses; Synaptic Cleft; Synaptic Transmission; System; TRPV1 gene; Testing; Vasopressins; Vesicle; Work; afferent nerve; electrical measurement; experience; improved; in vivo; insight; interest; neuronal cell body; neurotransmission; neurotransmitter release; patch clamp; presynaptic; programs; receptor; relating to nervous system; selective expression; size; synaptic depression; tool; transmission process

Beat to beat regulation of the cardiovascular system depends on an intact baroreflex. This reflex arc first synapses in the nucleus tractus solitarius (NTS) where glutamate is released. Baroreflex function is compromised in common life threatening disease states: hypertension, shock, and heart failure. Work in large, accessible CNS terminals suggests that the presynaptic control of glutamate release involves ion channels and 2nd messenger systems that regulate vesicle exocytosis. Glutamate regulation differs across neurons, but the mechanisms are poorly understood. Reflex pathways regulating the cardiovascular and respiratory systems depend on brainstem neurons and these reflexes are initiated by cranial nerve primary afferents acting within the nucleus tractus solitarius (NTS). Little is known about how primary afferents behave centrally. The small size of these terminals has made direct investigation difficult. We have developed methods to permit patch clamp recording from single nerve terminals in NTS. Our Research Plan will use these methods to address our driving hypothesis that important mechanisms of regulation in NTS depend on the identity of the afferent neuron. Our Preliminary Work demonstrates that NTS neurons offer a unique opportunity because: 1. we can directly visualize, identify, stimulate and electrophysiologically record from single nerve terminals, 2. NTS receives pharmacologically distinguishable afferent terminals that form subclasses known to arise from molecularly distinct peripheral neurons, 3. Subsets of these terminals can be labeled to provide links to functionally distinct afferents. Our Plan encompasses the efforts of two labs with complementary expertise suited to this problem. We will use direct patch recording and stimulation of single terminals, as well as imaging, to study the mechanism of frequency dependent synaptic depression and peptide modulation of glutamate release. The work capitalizes on using markers of primary afferent terminals to distinguish the various sub classes (TRPV1 and P2X3; C- and A-type afferent terminals, respectively). Specific Aims concern differential sodium, potassium and calcium channel expression across A- and C-type cranial afferent synaptic terminals plus the presence of new presynaptic mechanisms regulating synaptic cleft calcium. The different sub classes of afferent nerve terminal will be also be compared in terms of their control of glutamate release and modulation by peptides.

Beat击败心血管系统的调节取决于完整的BaroreFlex。这个反射弧首先 在释放谷氨酸的核片（NTS）中突触。 BaroreFlex函数是 在普通威胁生命的疾病状态中受到妥协：高血压，休克和心力衰竭。工作 大型，可访问的中枢神经系统端子表明，谷氨酸的突触前控制涉及离子 调节囊泡胞吐作用的通道和第二信使系统。谷氨酸调节差异 神经元，但这些机制知之甚少。反射途径调节心血管和 呼吸系统取决于脑干神经元，这些反射是由颅神经造成的 作用在核巨石核（NTS）中的传入。关于主要传入方式知之甚少 集中行动。这些终端的小尺寸使直接研究变得困难。我们有 开发了允许NTS中单神经终端记录贴片夹的方法。我们的研究计划 将使用这些方法来解决我们的驾驶假设，即NTS中的重要机制 取决于传入神经元的身份。我们的初步工作表明NTS神经元提供了 独特的机会是因为：1。我们可以直接可视化，识别，刺激和电生理记录 从单个神经末端，2。NTS接收到形成的药理学区分传入终端 已知的子类是由分子不同的周围神经元引起的，这些末端的子集可以是 标记以提供与功能不同传入的链接。我们的计划涵盖了两个实验室的努力 适合此问题的补充专业知识。我们将使用直接的贴片记录和刺激单一的刺激 终端以及成像，以研究依赖频率的突触抑制和 谷氨酸释放的肽调节。使用主要传入终端的标记的工作资本 为了区分各种子类（分别是TRPV1和P2X3； C-和A型传入终端）。 具体目的是涉及跨A和C型的差异钠，钾和钙通道表达 颅骨传入突触终端以及存在调节突触的新的突触前机制 钙。也将根据其不同的传入神经终端的子类别 控制谷氨酸释放和肽调节。