LIPIDS AND SIGNAL TRANSDUCTION IN NEURONS

该计划项目联合了5个独立实验室在 神经信号转导新机制的研究进展 突触效能的调节。尽管在以下方面取得了实质性进展 描述哺乳动物大脑的电路和细胞特性， 控制这些区域内突触强度变化的分子事件 电路现在才刚刚开始被理解。这项计划，有组织 分成3个单元，将使用生化、分子生物学和 阐明神经基本机制的电生理学方法 功能性和可塑性。大多数单位将把生化和 生理学研究，并将在这方面得到生物化学核心的协助。 自1985年以来，哥伦比亚大学神经科学家和 在二十烷类化合物生物合成方面经验丰富的生物化学家导致了 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器。未来的实验 将讨论二十碳烷类化合物的合成和功能以及相关的第二 交感神经元钙通道调节中的信使系统 (Siegelbaum&Role)及其在海兔神经元活动依赖性可塑性中的作用 (Feinmark&Schwartz)。大鼠海马区LTD4受体的表达 白三烯受体家族将被克隆(Axel)并详细 12-脂氧合酶衍生的生化和生理学研究 神经调节剂将继续存在(Feinmark&Schwartz)。调查结果： 简单的无脊椎动物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很好的逆行信使 长时程增强。另一方面，从生理上来说， 脊椎动物神经系统将帮助指导生物化学分析 海兔的这些小路。对学习、神经发展的新见解 和再生很可能是通过协调研究而出现的 在本计划中提出的。

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.