Physiology of Muscarinic Synapses in Sympathetic Ganglia

交感神经节毒蕈碱突触的生理学

• 批准号: 7224815
• 负责人: JOHN P HORN
• 金额: $ 31.95万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 1984
• 资助国家: 美国
• 起止时间: 1984-07-01 至 2010-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7224815
• 关键词: Acetylcholine; Adrenergic Agents; Amphibia; Amplifiers; Anatomy; Angiotensin II Receptor; Architecture; Autonomic ganglion; B-Lymphocytes; Behavior; Biological Models; Blood Pressure; Body Temperature; Cardiac; Cardiovascular Physiology; Cells; Cervical; Chromosome Pairing; Communication; Computer Simulation; Data; Development; Electrophysiology (science); Elements; Experimental Models; Feedback; Functional disorder; Ganglia; Gland; Goals; Heart Rate; Heart failure; Human; Hypertension; Lateral; Life; Measurement; Measures; Mediating; Methodology; Methods; Modeling; Molecular; Muscarinics; Myocardium; Myxoid cyst; Neuroanatomy; Neurons; Neuropeptides; Noise; Norepinephrine; Pathway interactions; Phenotype; Physiological; Physiology; Play; Preparation; Pressoreceptors; Process; Property; Rana catesbeiana; Rattus; Regulation; Research; Role; Scheme; Shapes; Signal Transduction; Smooth Muscle; Source; Stimulus; Structure of parasympathetic ganglion; Structure of superior cervical ganglion; Structure of thyroid parafollicular cell; Sympathetic Ganglia; Synapses; Synaptic plasticity; Syncope; System; Testing; Time; Tissues; Training; Varicosity; Vasoconstrictor Agents; Vasomotor; Work; adrenergic; base; cell type; concept; heart rhythm; motor control; neurophysiology; noradrenergic; novel; presynaptic; receptor; relating to nervous system; research study; virtual; voltage; voltage clamp

DESCRIPTION (provided by applicant): Sympathetic and parasympathetic ganglia provide the final common pathway for ail central motor control of smooth muscle, cardiac muscle and glands in tissues that mediate autonomic behavior. The long-term goals of this project are to determine how the neural architecture of autonomic ganglia enables them to transform spike trains, to elucidate how molecular and cellular mechanisms of synaptic plasticity shape this process, and to define the principles of ganglionic integration that contribute to behavior. The proposed work will focus upon modulatory muscarinic synapses in sympathetic ganglia, with emphasis on the subset of neurons that control cardiovascular function. The project will employ cellular neurophysiology, computational simulations, and neuroanatomy methods in 2 model systems - bullfrog sympathetic ganglia and the rat superior cervical sympathetic ganglion. Many of the physiological experiments will use the dynamic clamp method to implement virtual nicotinic synapses on living neurons and then determine how they interact with metabotropic neuromodulatory mechanisms. The analysis is predicated upon a working hypothesis that paravertebral sympathetic ganglia behave as variable synaptic amplifiers of activity whose gain is regulated by the strength and convergence of nicotinic synapses and by the expression of neuromodulatory mechanisms that serve to adjust the strength of nicotinic synapses. The specific aims are: 1) To contrast activity-dependent muscarinic gain modulation in 3 different sympathetic cell types. 2) To measure the contributions of quantal noise and presynaptic plasticity to synaptic gain. 3) To analyze the regulation of ganglionic integration by cardiac rhythms. 4) To test the hypothesis that metabotropic signaling through muscarinic, alpha-adrenergic and angiotensin II receptors provides a basis for phenotypic specialization of ganglionic integration in the rat SCG. Concepts developed through this research will contribute to fundamental understanding of normal autonomic behavior and human pathophysiology, especially to changes associated with syncope, hypertension and heart failure.

描述（由申请人提供）：交感神经和副交感神经神经节提供了介导自主行为的组织中平滑肌，心脏肌肉和腺体的中央运动控制的最终公共途径。该项目的长期目标是确定自主神经节的神经结构如何使它们能够改变尖峰火车，以阐明突触可塑性的分子和细胞机制如何塑造此过程，并定义有助于行为的神经节整合的原理。拟议的工作将集中于交感神经节中的调节毒蕈碱突触，重点是控制心血管功能的神经元子集。该项目将在2个模型系统中采用细胞神经生理学，计算模拟和神经解剖学方法 - 牛蛙交感神经节和大鼠上宫颈交感神经节。许多生理实验将使用动态夹具方法来实现活神经元的虚拟烟碱突触，然后确定它们与代谢性神经调节机制的相互作用。该分析是基于一个有效的假设，即副脑交感神经神经节作为活性的可变突触放大器，其增益受烟碱突触的强度和收敛性调节，并通过神经调节机制的表达来调节烟碱突触的强度。具体目的是：1）在3种不同的交感细胞类型中对比依赖活性的毒蕈碱增益调节。 2）测量量子噪声和突触前可塑性对突触增益的贡献。 3）分析通过心律对神经节整合的调节。 4）测试假说，即通过毒蕈碱，α-肾上腺素能和血管紧张素II受体的代谢信号传导为大鼠SCG中神经节整合的表型专业化提供了基础。通过这项研究发展的概念将有助于对正常自主行为和人类病理生理学的基本理解，尤其是与晕厥，高血压和心力衰竭相关的变化。