NEUROTROPHINS IN CORTICAL DEVELOPMENT AND COMPLETION

描述：在哺乳动物的视觉系统中，神经元活动施加 对正常所需电路的发展产生强大的影响 幻象。早期生活中特定形式的视觉体验，例如 单眼剥夺，导致大脑皮层能力不可挽回的变化 来处理视觉信息。关于活动在…中的作用的几个理论 皮质发育表明来自外侧膝状核的输入 (LGN)以依赖活动的方式竞争限制数量 在皮质发育过程中存在一些因素。建议的总体目标是 研究是确定神经营养素是否符合标准 对他们来说是必要的这些因素。一项基本要求 在这种情况下，神经营养因子的作用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因子的新方法相结合 从切片中解决这个问题。接下来的一系列实验将 确定特定神经营养因子的局部增强或耗竭 挽救或复制单眼优势转移的影响， 和取向选择性的保持。要评估这些影响，请使用 神经营养因子包被的神经营养因子局部给药新方法 乳胶微球，将与最后一组实验相结合，一个 脑片短期培养与颗粒介导基因相结合 神经营养素水平的转移和操作将用于评估 神经营养因子与神经元活动在修饰中的相互作用 第四层中的树枝。这些实验加在一起，应该 提供神经营养因子在皮质发育中作用的关键测试。 这反过来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外伤性衰竭的疾病 皮质环路的生长。

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.