NEW NEURONS AND NEW SYNAPSES

该提案描述了对添加新神经元的研究， 突触连接的重组发生在 金鱼胚后发育过程中的视觉系统。 先前的工作已经 显示棒是从特殊的前体细胞中产生的， 即使在成年人中也会插入分化的视网膜。 拟议 研究试图发现新的杆是如何整合到 预先建立的视网膜回路，什么是功能的后果， 视杆细胞发育的延迟和延长， 控制正常和再生视网膜中的神经发生。 有五个具体目标。 1.为了描述突触发生， 金鱼幼鱼和幼鱼视网膜中的感光细胞（视杆）。 2.检查视网膜反应的发展，并确定 涉及的神经回路 3.来研究 米勒神经胶质细胞和迁移神经元前体。 4.以确定是否 机械拉伸调节视网膜中细胞增殖的速率 以及是否与细胞死亡有关。 5.为了检查 杆前体细胞群，并挑战 当视网膜再生时， 在被代谢毒素破坏之后。 这些实验与发展中的两个中心问题有关。 神经生物学 第一个问题是：神经元如何适应 与它们一起形成的其他神经元的相对数量或比例 关系？ 第二个是：神经元之间的细胞相互作用 和神经胶质细胞影响大脑结构的发育 的 对视网膜再生的研究也将提供重要的信息 关于中枢神经系统中神经元的修复和替换。

This proposal describes investigations into the addition of new neurons and the resultant reorganizations of synaptic connectivity which occur in the visual system during postembryonic growth of goldfish. Previous work has shown that rods are produced from special precursor cells and continuously inserted into the differentiated retina even in adults. The proposed studies seek to discover how the new rods are integrated into the preestablished retinal circuitry, what are the functional consequences of the delayed and prolonged development of rods, and what are the rules that govern neurogenesis in the normal and regenerating retina. There are five Specific Aims. 1. To describe synaptogenesis of photoreceptor cells (rods) in the larvae and juvenile retina of goldfish. 2. To examine the development of the retinomotor response and to determine the neural circuitry involved. 3. To examine the relationship between Muller glia and migrating neuronal precursors. 4. To determine whether mechanical stretch modulates the rate of cell proliferation in the retina and whether cell death is involved. 5. To examine the specificity of the rod precursors population using immunocytochemistry and to challenge the rod precursors to lose their specificity when the retina regenerates following destruction by metabolic toxins. These experiments are relevant to two central issues in developmental neurobiology. The first is: how do neurons adjust to changes in the relative numbers or proportions of other neurons with which they form connections? The second is: how do cellular interactions between neurons and glial cells influence the development of structure in the brain? The studies on retinal regeneration will also provide important information about repair and replacement of neurons in the central nervous system.