MEMBRANE PROPERTIES OF NEOCORTICAL NEURONS

新皮质神经元的膜特性

• 批准号: 3397126
• 负责人: WAYNE E. CRILL
• 金额: $ 19.5万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 1982
• 资助国家: 美国
• 起止时间: 1982-04-01 至 1995-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3397126
• 关键词: biological signal transduction; brain cell; calcium channel; cats; central nervous system; cholecystokinin; electrophysiology; mathematical model; membrane permeability; membrane structure; motor cortex; muscarine; neural information processing; neurons; neuropeptides; neuropharmacology; norepinephrine; potassium channel; second messengers; sensory cortex; synapses; vasoactive intestinal peptide; voltage /patch clamp

Our objective is to understand the mechanisms of intercellular communication between neurons in the mammalian central nervous system. We focus on the roles played by postsynaptic membrane conductances in the transduction of chemically- mediated synaptic signals into spike trains. Our experiments will use isolated neocortical brain slices, dissociated adult neurons, intracellular recording, single electrode voltage clamp and patch clamp techniques. We will use voltage clamp, pharmacological blocking agents and a mathematical model to test hypotheses about the functions of five identified K+ currents. Our experiments have revealed that muscarine and norepinephrine decrease the same two K+ currents in neocortical cells, and the proposed studies are designed to further elucidate the mechanism whereby two apparently different second messenger systems mediate a similar physiological action. We will study the action of the neuropeptide modulators vasoactive intestinal polypeptide and cholecystokinin octapeptide sulfate. By isolating the dendrites from the soma and using dissociated adult neurons, we will identify the location and properties of Ca2+ currents in neocortical cells. These studies will answer fundamental questions about the mechanisms involved in synaptic communication between neurons. The specific neurons studied are those giving rise to the primary motor output of cerebral cortex. The results of these experiments will serve as a foundation for formulating hypotheses about epileptic mechanisms in neocortex and will contribute to our understanding of diseases such as amyotrophic lateral sclerosis and Alzheimer's disease.

我们的目标是了解细胞间的机制 哺乳动物中央神经元之间的沟通 神经系统。 我们专注于突触后扮演的角色 化学转导的膜电导 将突触信号介导了尖峰火车。 我们的实验会 使用孤立的新皮层脑切片，解离的成年神经元， 细胞内记录，单电极电压夹和斑块 夹具技术。 我们将使用电压夹，药理 阻止代理和数学模型来检验假设 关于五个已识别的K+电流的功能。 我们的 实验表明，毒方法和去甲肾上腺素 减少新皮质细胞中相同的两个K+电流，并降低 拟议的研究旨在进一步阐明机制 有两个显然不同的第二会系统 介导类似的生理作用。 我们将研究 神经肽调节剂血管活性肠多肽和 胆囊动蛋白八肽硫酸盐。 通过隔离树突 从soma并使用解离的成年神经元，我们将 确定Ca2+电流的位置和特性 新皮层细胞。 这些研究将回答基本 有关突触中涉及的机制的问题 神经元之间的沟通。 研究的特定神经元 那些引起大脑的主要电动机输出 皮质。 这些实验的结果将作为 制定有关癫痫机制的假设的基础 在新皮层中，将有助于我们对疾病的理解 例如肌萎缩性侧索硬化症和阿尔茨海默氏病。