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.

心血管系统的逐搏调节依赖于完整的压力反射。这个反射弧首先 孤束核（NTS）中的突触，谷氨酸在此释放。压力反射功能是 在常见的危及生命的疾病状态中受损：高血压、休克和心力衰竭。工作 大的、可接近的中枢神经系统末梢表明，突触前谷氨酸释放的控制涉及离子 通道和第二信使系统，调节囊泡胞吐作用。谷氨酸调节在不同的 神经元，但机制知之甚少。调节心血管和 呼吸系统依赖于脑干神经元，这些反射是由脑神经初级 孤束核（NTS）内的传入神经。关于初级传入神经 行为集中。这些码头的面积很小，直接调查很困难。我们有 开发的方法，允许膜片钳记录从单一的神经末梢在NTS。我们的研究计划 我将使用这些方法来解决我们的驱动假说，即重要的调节机制，在NTS 取决于传入神经元的身份。我们的初步工作表明，NTS神经元提供了一个 独特的机会，因为：1。我们可以直接观察，识别，刺激和电生理记录 从单个神经末梢，2. NTS接收可区分的传入终末， 已知从分子上不同的外周神经元产生的亚类，3.这些终端的子集可以是 标记为提供到功能上不同的传入的链接。我们的计划包括两个实验室的努力， 适合这个问题的补充专业知识。我们将使用直接的补丁记录和刺激的单一 终末，以及成像，以研究频率依赖性突触抑制的机制， 谷氨酸释放的肽调节。这项工作利用初级传入终末的标记 以区分各种亚类（TRPV 1和P2 X3;分别为C型和A型传入末梢）。 具体目的涉及A型和C型之间的差异钠、钾和钙通道表达 颅传入突触终末加上新的突触前机制的存在，调节突触 缺钙还将比较传入神经末梢的不同亚类在它们的 谷氨酸释放的控制和肽的调节。