Presynaptic Mechanisms of Neurotransmission in NTS

NTS 中神经传递的突触前机制

• 批准号: 7569353
• 负责人: Michael Christian Andresen
• 金额: $ 35.79万
• 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 2010-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7569353
• 关键词: Address; Afferent Neurons; Automobile Driving; Axon; Baroreflex; Brain Stem; Calcium; Calcium Channel; Cardiovascular system; Cephalic; Characteristics; 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; 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; 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.

搏动对心血管系统的调节依赖于完整的气压反射。首先是反射弧