Physiology of Muscarinic Synapses in Sympathetic Ganglia

交感神经节和副交感神经节为所有中枢运动控制提供了最终的共同通路。 平滑肌、心肌和调节自主行为的组织中的腺体。远景目标 这个项目的目的是确定自主神经节的神经结构如何使它们能够转换 为了阐明突触可塑性的分子和细胞机制如何塑造这一过程， 并确定神经节整合的原则，有助于行为。拟议的工作将 重点是交感神经节中的调节性毒蕈碱突触，重点是神经元的子集 控制着心血管功能该项目将采用细胞神经生理学，计算 模拟和神经解剖学方法在两个模型系统-牛蛙交感神经节和大鼠 上级颈交感神经节。许多生理学实验都会用到动力钳 一种在活神经元上实现虚拟烟碱突触的方法，然后确定它们如何与 代谢性神经调节机制。该分析基于一个工作假设， 椎旁交感神经节表现为活动的可变突触放大器，其增益受到调节 通过烟碱突触的强度和会聚以及神经调节因子的表达， 调节烟碱突触强度的机制。具体目的是：1）对比 活性依赖性毒蕈碱增益调制在三种不同的交感神经细胞类型。2)测量 量子的贡献！噪声和突触前可塑性突触增益。3)分析了 通过心脏节律的神经节整合。4)为了验证这一假设， 毒蕈碱、α-肾上腺素能和血管紧张素II受体为表型特化提供了基础。 大鼠SCO中的神经节整合。通过这项研究开发的概念将有助于 对正常自主行为和人类病理生理学的基本理解，特别是 与晕厥、高血压和心力衰竭相关的变化。

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 two 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 three different sympathetic cell types. 2) To measure the contributions of quanta! 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 SCO. 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.