FACTORS REGULATING LIMBIC SYSTEM ASSEMBLY

调节边缘系统组装的因素

• 批准号: 2246628
• 负责人: PAT LEVITT
• 金额: $ 23.86万
• 依托单位: UNIV OF MED/DENT NJ-R W JOHNSON MED SCH
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-09-01 至 1999-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2246628
• 关键词: antibody formation; axon; brain cell; cell differentiation; developmental neurobiology; hippocampus; laboratory mouse; laboratory rabbit; laboratory rat; limbic system; membrane proteins; molecular cloning; monoclonal antibody; neuroanatomy; neurotransmitters; protein purification; protein sequence; tissue /cell culture; transplantation

The goals of this project are to determine the factors that regulate the differentiation neurons comprising the mammalian limbic system and to define the molecular mechanisms that mediate the formation of functional neural circuits during development. Our laboratory is most interested in gaining a basic understanding of these mechanisms in those parts of the mammalian central nervous system that mediate emotional behavior, memory and learning. We will characterize the role of cell surface proteins in the formation of connections, focusing prinicipally on the limbic system associated membrane protein (LAMP), 64,000 dalton glycoprotein isolated in our laboratory that is expressed early in development and may in part regulate the formation of limbic system connections. We propose 3 sets of experiments that will examine different aspects of the development of this system: 1) The role of LAMP and macromolecules carrying the HNK-1 carbohydrate epitope in the regulation of process differentiation and the innervation of targets by limbin neurons will continue to be evaluation in both roller tube explant and monolayer culture systems. 2) LAMP expression will be used as a marker in cortical transplant studies to evaluate the intrinsic and extrinsic factors that may mediate the commitment and differentiation of neurons destined for specific limbic cortical areas. 3) Molecular characterization of LAMP will continue by analyzing metabolic changes in LAMP during axonal growth and by purifying substantial amounts of LAMP to generate new mono- and polyclonal antibodies and in a collaborrative effort, deduce partial sequence information. In a second collaborative arrangement, we will perform expression library screening to isolate and clone the LAMP gene for subsequent sequence analysis and in situ localization of neurons expressing the LAMP gene. These basic developmental studies employ a variety of technical approaches, both anatomical and molecular, to address basic issues of neural circuit formation. Our long-term goal is to utilize this information to determine how developmental defects may result in specific behavioral abnormalities, and ultimately how these may be corrected.

该项目的目标是确定调节因素 分化神经元包括哺乳动物边缘系统和 定义介导功能形成的分子机制 发育过程中的神经回路。我们实验室最感兴趣的是 对这些部分的这些机制有基本的了解 哺乳动物中枢神经系统，调节情绪行为、记忆 和学习。我们将描述细胞表面蛋白在 连接的形成，主要集中在边缘系统 相关膜蛋白 (LAMP)，分离的 64,000 道尔顿糖蛋白 在我们的实验室中，它在发育早期就表达出来，可能部分地 调节边缘系统连接的形成。我们建议3套 实验将检验发展的不同方面 该系统：1）LAMP和携带HNK-1的大分子的作用 碳水化合物表位在调节过程分化和 将继续评估边缘神经元对目标的神经支配 在滚管外植体和单层培养系统中。 2) 灯 表达将被用作皮质移植研究中的标记 评估可能介导的内在和外在因素 特定边缘系统神经元的定型和分化 皮质区域。 3) LAMP 的分子表征将继续进行 分析轴突生长过程中 LAMP 的代谢变化并通过纯化 大量的 LAMP 以产生新的单克隆和多克隆 抗体并共同努力推导出部分序列 信息。在第二次合作安排中，我们将表演 筛选表达库以分离和克隆 LAMP 基因 随后的序列分析和神经元的原位定位 表达 LAMP 基因。 这些基础发展研究采用了各种技术 解剖学和分子学方法来解决基本问题 神经回路的形成。我们的长期目标是利用这一点 确定发育缺陷如何导致特定的信息 行为异常，以及最终如何纠正这些异常。