NEUROTROPHINS IN CORTICAL DEVELOPMENT AND COMPLETION

神经营养因子在皮质发育和完成中的作用

• 批准号: 2444388
• 负责人: DONALD C LO
• 金额: $ 19.41万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-07-01 至 2000-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2444388
• 关键词: afferent nerve; bioassay; brain; cell differentiation; dendrites; developmental neurobiology; ferrets; genetically modified animals; histogenesis; laboratory mouse; lateral geniculate body; neural plasticity; neurons; neurotrophic factors; organ culture; transfection; visual cortex

DESCRIPTION: In the mammalian visual system, neuronal activity exerts a powerful influence on the development of circuits required for normal vision. Specific forms of visual experience during early life, such as monocular deprivation, lead to irrevocable changes in the cortex's ability to process visual information. Several theories for the role of activity in cortical development propose that inputs from the lateral geniculate nucleus (LGN) compete, in an activity-dependent manner, for limiting quantities of some factor present in developing cortex. The overall goal of the proposed research is to determine whether neurotrophins fulfill the criteria necessary for them to be these factors. A fundamental requirement for neurotrophins to function in this context is that their release be regulated by neuronal activity. In the first series of experiments, sensitive bioassays will be combined with a new method for extracting neurotrophins from slices to address this issue. The next series of experiments will determine whether local augmentation or depletion of specific neurotrophins rescues or replicates the effects of monocular shifts in ocular dominance, and the preservation of orientation selectivity. To assess these effects, a new method for local delivery of neurotrophins, based on neurotrophin-coated latex microspheres, will be combined with the final group of experiments, a combination of short-term cultures of brain slices, particle-mediated gene transfer, and manipulations of neurotrophin levels will be used to assess the interactions between neurotrophins and neuronal activity in modifying dendritic arbors in layer 4. Taken together, these experiments should provide critical tests of the role of neurotrophins in cortical development. This in turn could lead to the design of rational therapies for amblyopia and other disorders involving congenital or trauma-induced failures in growth of cortical circuits.

描述：在哺乳动物的视觉系统中，神经元活动产生一种 强大的影响力的发展所需的电路正常 视野 早期生活中的特定视觉体验形式，例如 单眼剥夺，导致大脑皮层的能力发生不可挽回的变化， 来处理视觉信息。 关于活动作用的几种理论 皮质发育表明来自外侧膝状体核输入 (LGN)以活动依赖的方式竞争有限数量的 一些存在于发育中皮层中的因子。 拟议的总体目标 研究是为了确定神经营养因子是否符合标准 这些因素是必要的。 的根本要求 在这种情况下，神经营养因子发挥作用的一个重要原因是它们的释放受到调节， 通过神经元活动。 在第一系列实验中，敏感的 生物测定将与提取神经营养素的新方法相结合 来解决这个问题。 接下来的一系列实验将 确定特定神经营养因子的局部增加或减少 挽救或复制单眼优势转移的效果， 以及保持取向选择性。 为了评估这些影响， 基于神经营养素包被的神经营养素局部递送的新方法 乳胶微球，将与最后一组实验相结合， 结合短期培养的脑片，颗粒介导的基因 转移和神经营养因子水平的操作将用于评估 神经营养因子和神经活性之间的相互作用， 第4层为树枝状乔木。 综合起来，这些实验应该 提供关键测试的作用，神经营养素在皮质发育。 这反过来又可能导致设计合理的弱视治疗方法 以及其他涉及先天性或创伤引起的 皮层回路的增长