PHYSIOLOGY OF MUSCARINIC SYNAPSES IN SYMPATHETIC GANGLIA

本计画的长期目标是阐明整合功能 牛蛙交感神经节中的毒蕈碱和肽能突触。 牛蛙之所以被选中进行研究，是因为它的解剖特征是 最适合于电生理学实验，可以在 细胞水平，直接关系到血管张力的控制， 腺体分泌 所提出的实验利用了椎旁交感神经 牛蛙中的神经元被组织成两个主要的子系统，B和C， 可以通过轴突传导速度来识别， 由于它们的解剖分离， 节前输入 这些细胞类型通过它们的 毒蕈碱突触和神经肽的表达，并通过其 功能角色。实验将采用电生理学方法 研究含有神经节及其 终末器官，单独的神经节，或单独的终末器官，并研究分离的 原代细胞培养中的神经元。 该提案有三个具体目标： 1)为了验证共递质赋予血管紧张素C系统的假设， 具有可变的突触增益，其由突触的时间模式调节 节前活动 这个假设的模型假定， 神经节和终末器官用作串联的2个可变增益级。 在神经节中，乙酰胆碱（ACH）和促黄体生成素释放激素 （LHRH）共同释放以产生烟碱epsp，缓慢毒蕈碱ipsp， 和慢肽能EPSP。 两个慢波之间的时间相互作用 假设突触电位控制神经节增益。 在 外围，据推测，共发射器的释放 肾上腺素（EPI）和神经肽Y（NPY）的差异调节， 活动 当NPY被释放时，它通过增强 血管对肾上腺素的反应 2)为了验证B系统支配皮肤粘膜的假设， 降钙素基因相关肽（CGRP）是一种神经节细胞， 介导慢EPSP的共递质和营养因子， 调节烟碱ACH受体的表达。 3)为了验证神经节前C纤维释放的LHRH是否起作用， 异突触地增加突触前和突触后之间的突触增益。 节后B神经元。 拟议研究的结果将提供一个概念框架， 了解突触共传递的整合功能， 包括哺乳动物自主神经节和大脑在内的复杂回路。

The long-term goal of this project is to elucidate the integrative function of muscarinic and peptidergic synapses in bullfrog sympathetic ganglia. The bullfrog was chosen for study because its anatomical features are optimal for electrophysiological experiments that can be performed at the cellular level and directly related to the control of vascular tone and glandular secretion. The proposed experiments exploit the fact that paravertebral sympathetic neurons in the bullfrog are organized into 2 major subsystems, B and C, that can be identified by their axonal conduction velocities, and selectively activated due to the anatomical separation of their preganglionic inputs. These cell types are further distinguished by their expression of muscarinic synapses and neuropeptides, and by their functional roles. The experiments will employ electrophysiological methods to study isolated preparations containing either ganglia and their end-organs, ganglia alone, or end-organs alone, and to study dissociated neurons in primary cell culture. The proposal has 3 specific aims: 1) To test the hypothesis that co-transmitters endow the vasomotor C system with variable synaptic gain that is regulated by temporal patterns of preganglionic activity. The hypothetical model postulates that synapses in the ganglia and at end-organs function as 2 variable gain stages in series. In ganglia, acetylcholine (ACH) and luteinizing hormone releasing hormone (LHRH) are co-released to produce a nicotinic epsp, a slow muscarinic ipsp, and a slow peptidergic epsp. Temporal interactions between the 2 slow synaptic potentials are hypothesized to control ganglionic gain. In the periphery, it is postulated that the release of the co-transmitters epinephrine (EPI) and neuropeptide Y (NPY) is differentially regulated by activity. When NPY is released, it enhances end-organ gain by potentiating vascular responses to EPI. 2) To test the hypotheses that the B system innervates cutaneous mucous glands and that calcitonin gene-related peptide (CGRP) is both a ganglionic co-transmitter that mediates a slow epsp and a trophic factor that regulates the expression of nicotinic ACH receptors. 3) To test the hypothesis that LHRH released by preganglionic C fibers acts heterosynaptically to increase the gain of synapses between pre- and postganglionic B neurons. Results of the proposed studies will provide a conceptual framework for understanding the integrative function of synaptic co-transmission in more complex circuits including mammalian autonomic ganglia and the brain.