CELLULAR PHYSIOLOGY OF CORTICAL DEVELOPMENT

描述(逐字摘自申请者摘要)：本项目地址 脑内突触形成的基本分子和细胞生物学机制 哺乳动物中枢神经系统(CNS)。这项研究将使用新的光学 成像方法和各种分子和生理干预 大鼠海马区培养中突触发生的早期研究 神经元。我们提出的实验将解决三组问题：1. 什么是细胞运动和生长过程启动物理细胞-细胞接触？ 突触组装的特定位置，以及这些运动机制是如何 调节？2.细胞黏附分子(特别是细胞黏附分子的成员 钙粘蛋白超家族)在维持突触接触和触发中的作用 突触组装？3.粘着、突触前活动区的动力学是什么 细胞-细胞接触后的组装和新生突触前功能 突触部位？这项工作将提供有关的基本新信息 目前尚不清楚中枢神经系统突触形成的机制。此信息 应该说明负责正常和病理的过程 神经系统的发育和生长，尤指 突触电路拓扑图。解决电的影响的实验 突触发生的活动和神经递质应该有助于解释 体验影响大脑发育，还可能提供对 新突触形成在学习和记忆中的可能作用。这部作品 还应有助于制定合理的战略，以促进中央 创伤后神经系统的再生和功能的恢复 卒中。

DESCRIPTION (Verbatim from the Applicant's Abstract): This project addresses basic molecular and cell biological mechanisms of synapse formation in the mammalian central nervous system (CNS). This research will use novel optical imaging methods and a wide variety of molecular and physiological interventions to explore early stages of synaptogenesis in cultures of rat hippocampal neurons. The experiments we propose will address three sets of questions: 1. What cell motility and growth processes initiate physical cell-cell contact at specific sites of synapse assembly, and how are these motility mechanisms regulated? 2. What roles cell adhesion molecules (particularly members of the cadherin superfamily) play in sustaining synaptogenic contact and triggering synapse assembly? 3. What are the dynamics of adhesion, presynaptic active zone assembly and nascent presynaptic function following cell-cell contact at synaptic sites? This work will provide fundamental new information about presently unexplored mechanisms of CNS synapse formation. This information should illuminate the processes responsible for both normal and pathological development and growth of the nervous system, especially the creation of synaptic circuit topologies. Experiments addressing effects of electrical activity and neurotransmitters on synaptogenesis should help explain how early experience effects brain development and may also provide insights into possible roles of new synapse formation in learning and memory. This work should also help in efforts to devise rational strategies to promote central nervous system regeneration and recovery of function following trauma and stroke.