LIPIDS AND SIGNAL TRANSDUCTION IN NEURONS

神经元中的脂质和信号转导

• 批准号: 3100373
• 负责人: STEVEN J FEINMARK
• 金额: $ 77.55万
• 依托单位: COLUMBIA UNIV NEW YORK MORNINGSIDE
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-05-01 至 1997-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3100373
• 关键词: biological signal transduction; lipid metabolism; neurophysiology

This Program Project unites the efforts of 5 independent laboratories in studies of novel mechanisms of neural signal transduction and the modulation of synaptic efficacy. Despite substantial progress in describing the circuitry and cellular properties of the mammalian brain, the molecular events that control changes in synaptic strength within these circuits are only now beginning to be understood. This Program, organized into 3 Units, will use biochemical, molecular biological and electrophysiological methods to elucidate basic mechanisms of neural function and plasticity. Most Units will combine biochemical with physiologic studies and will be assisted in this by the Biochemistry Core. Since 1985, the joint efforts of Columbia University neuroscientists and biochemists experienced in eicosanoid biosynthesis have led to the recognition that arachidonic acid and its metabolites function as modulators in both vertebrate and invertebrate neurons. Future experiments will address the synthesis and function of eicosanoids and related second messenger systems in modulation of Ca2+ channels in sympathetic neurons (Siegelbaum & Role) and in activity-dependent plasticity in Aplysia neurons (Feinmark & Schwartz). The hippocampal LTD4 receptor (as a model for a family of leukotriene receptors will be cloned (Axel) and detailed biochemical and physiologic studies of 12-lipoxygenase-derived neuromodulators will continue (Feinmark & Schwartz). Results from the simple invertebrate nervous system will continue to suggest appropriate research directions in the mammalian brain. For example, they suggest that arachidonate metabolites are good candidates as retrograde messengers in long-term potentiation. On the other hand, physiological results from the vertebrate neural systems will help direct the biochemical analyses of these pathways in Aplysia. New insights into learning, neural development and regeneration are likely to emerge from the coordinated research proposed in this Program.

该计划项目联合了5个独立实验室的努力， 神经信号转导新机制的研究及神经元的功能 突触功效的调节。 尽管取得了重大进展， 描述了哺乳动物大脑的电路和细胞特性， 控制突触强度变化的分子事件 电路现在才开始被理解。 该计划，组织 分为3个单元，将使用生物化学，分子生物学和 电生理学方法来阐明神经的基本机制 功能和可塑性。 大多数单位将联合收割机与生物化学相结合 生理学研究，并将在这方面的生物化学核心协助。 自1985年以来，哥伦比亚大学神经科学家和 在类花生酸生物合成方面经验丰富的生物化学家已经导致了 认识到花生四烯酸及其代谢物的功能， 脊椎动物和无脊椎动物神经元中的调节剂。 未来的实验 将讨论类二十烷酸的合成和功能以及相关的第二 交感神经元钙通道的信使系统 （Siegelbaum & Role）和在失智症神经元的活动依赖性可塑性中的作用 （Feinmark & Schwartz）. 海马LTD 4受体（作为一个模型， 将克隆一个白三烯受体家族（阿克塞尔）并详细说明 12-脂氧合酶衍生的生物化学和生理学研究 神经调节剂将继续（Feinmark & Schwartz）。 结果 简单的无脊椎神经系统将继续建议适当的 哺乳动物大脑的研究方向。 例如，他们建议， 花生四烯酸代谢物是逆行信使的良好候选者， 长时程增强 另一方面，生理结果从 脊椎动物神经系统将有助于指导生物化学分析， 这些途径在亚洲。 对学习和神经发育的新见解 和再生可能会出现在协调研究中， 在这个方案中提出。