DEVELOPMENT AND FUNCTION OF SYNAPTIC COTRANSMISSION

突触协同传递的发育和功能

• 批准号: 2259286
• 负责人: JOHN P HORN
• 金额: $ 7.18万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-12-01 至 1994-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2259286
• 关键词: RNA; Rana; acetylcholine; alternatives to animals in research; calcitonin gene related peptide; cell differentiation; electrophoresis; electrophysiology; epinephrine; gene expression; gonadotropin releasing factor; in situ hybridization; neural transmission; neurogenesis; neuropeptide Y; neuropeptide receptor; neuropeptides; neurotransmitter metabolism; nucleic acid hybridization; substance P; sympathetic ganglion; synaptogenesis; tissue /cell culture

The objectives of this application are to intensify ongoing research on the physiology of synaptic cotransmission in sympathetic ganglia and to learn molecular and biological methods that will be applied in new studies of neuronal differentiation. The P.I. is an assistant professor of Physiology and is in the 05 year of independent research with RO1 support. An excellent collegial environment and adequate support services exist within the local University community. The propose plan will insure continued development of the P.I.'s research career. It will limit growth of non-research related activities and provide resources to pursue new methodologies, experiments and collaborations. The experiments will utilize a combination of electrophysiological, anatomical and biochemical methods in isolated preparations and in primary cell cultures. The new methods to be learned include nucleic acid isolation,Northern analysis and in situ hybridization. The experimental goals of the proposal are to determine the integrative function and the developmental origins of synapses that utilize slowly acting peptidergic co-transmitters in addition to the classical transmitters acetylcholine (ACH) and epinephrine (EPI). The roles of 4 neuropeptides, luteinizing hormone releasing hormone (LHRH), neuropeptide Y (NPY), calcitonin gene-related peptide (CGRP) and substance P (SP), will be analyzed in the sympathetic system of bullfrog. Although these peptides are co-expressed with other transmitters in many regions of the peripheral and central nervous system, the functional dynamics and ontogeny of synaptic co-transmission is largely unknown. Bullfrog sympathetic ganglia express a diversity of synaptic mechanisms and yet they are accessible to analysis at the cellular and molecular levels. In the lumbar ganglia, there exist 3 subclasses of sympathetic neurons that can be distinguished by their functions, electrophysiological properties, connectivity with the spinal cord and with peripheral targets, and by their expression of muscarinic cholinergic receptors and neuropeptides. In the vasomotor sympathetic C system, LHRH and ACH are co-released by preganglionic neurons and elicit 3 postsynaptic potentials in a subset of ganglion cells that co-express EPI and NPY-like immunoreactivity. The first specific aim of this proposal is to test the hypothesis that co-transmission at ganglionic and end-organ synapses in this circuit enhances the dynamic range of vascular contractions that can be elicited by different patterns of preganglionic stimulation. The second specific aim is to test the hypothesis that CGRP is co-released with ACH by preganglionic B neurons and produces trophic effects and an excitatory postsynaptic potential in B neurons. The third goal is to establish the timetable during development in tadpoles for cell-specific expression of neuropeptide genes and their products. Using tissue culture, the final goal of the project will be to test the hypothesis that expression of NPY is controlled by molecules in the extracellular environment and/or by cellular interactions, and that such factors also control the electrophysiological differentiation of vasomotor neurons.

本申请的目的是加强正在进行的研究

项目成果

A presynaptic mechanism accounts for the differential block of nicotinic synapses on sympathetic B and C neurons by d-tubocurarine.

突触前机制解释了 d-筒箭毒碱对交感 B 和 C 神经元烟碱突触的差异阻滞。

• DOI: 10.1523/jneurosci.15-07-05025.1995
• 发表时间: 1995
• 期刊: The Journal of neuroscience : the official journal of the Society for Neuroscience.
• 作者: Shen,WX;Horn,JP
• 通讯作者: Horn,JP

The sensitivity of nicotinic synapses in bullfrog sympathetic ganglia to alpha-bungarotoxin and neuronal-bungarotoxin.

牛蛙交感神经节烟碱突触对α-银环蛇毒素和神经元银环蛇毒素的敏感性。

• DOI: 10.1111/j.1476-5381.1994.tb17077.x
• 发表时间: 1994
• 期刊: British journal of pharmacology
• 影响因子: 7.3
• 作者: Shen,WX;Jobling,P;Horn,JP
• 通讯作者: Horn,JP

Preganglionic and sensory axons in developing bullfrog sympathetic ganglia express three neuropeptides during early tadpole stages.

发育中的牛蛙交感神经节的节前轴突和感觉轴突在蝌蚪早期阶段表达三种神经肽。

• DOI: 10.1016/0165-1838(91)90022-u
• 发表时间: 1991
• 期刊: Journal of the autonomic nervous system
• 作者: Stofer,WD;Horn,JP
• 通讯作者: Horn,JP

Expression of neuropeptide-Y-like immunoreactivity begins after adrenergic differentiation and ganglionic synaptogenesis in developing bullfrog sympathetic neurons.

在发育中的牛蛙交感神经元中，肾上腺素能分化和神经节突触发生后，神经肽 Y 样免疫反应性开始表达。

• DOI: 10.1523/jneurosci.10-10-03305.1990
• 发表时间: 1990
• 期刊: The Journal of neuroscience : the official journal of the Society for Neuroscience
• 作者: Stofer,WD;Horn,JP
• 通讯作者: Horn,JP

The undergraduate medical curriculum: centralized versus departmentalized.

本科医学课程：集中与部门化。

• DOI: 10.1097/00001888-199508000-00007
• 发表时间: 1995
• 期刊: Academic medicine : journal of the Association of American Medical Colleges
• 作者: Reynolds3rd,CF;Adler,S;Kanter,SL;Horn,JP;Harvey,J;BernierJr,GM
• 通讯作者: BernierJr,GM