NEURON DEATH IN CENTRAL NERVOUS SYSTEM DEVELOPMENT

新皮层的内在组织的本质是一个中央的 发育神经生物学的问题。 成熟的大脑皮层是一个马赛克 功能和解剖学上的专门区域， 基本层状和柱状结构。 核心问题是 新皮层是否是一个未指定的统一结构， 身份是由丘脑等外部机构强加的， 包含内在的地方身份，吸引和组织特定的 输入结构并指定某些输出。的发展 丘脑向皮质投射的切线和层状特异性 将在两个实验条件下进行研究。 上 实验中，背侧新皮层的一个区域，主要是视觉皮层，将 在第一个丘脑轴突到达之前， 皮质，以及发育、存活、成熟投射模式和 将研究丘脑轴突的乔木体积。 在第二 操纵，第四层的发展删除和变化 大量的颗粒上层将使用有丝分裂 抑制剂，MAM（甲基偶氮甲醇乙酸酯），并进行平行分析。 这两种操作的目的都是删除目标 在轴突和靶群体的任何相互作用之前， 从而揭示任何内在的特异性，在选择皮质和 层终端区传入丘脑皮质轴突，和 丘脑和皮层之间的人口匹配机制。 的 这项工作的临床意义是直接的：除了提供 脑损伤后皮质重组的基本信息 损伤后，我们将直接描述皮层发生了什么， 早期局部缺失，例如可能发生血管意外，或 在细胞毒性损伤之后。

The nature of the intrinsic organization of the neocortex is a central question in developmental neurobiology. The mature neocortex is a mosaic of functionally and anatomically specialized areas that share a fundamental laminar and columnar structure. The central question is whether the neocortex is an unspecified, unified structure on which local identity is imposed by an external agency like the thalamus or whether it contains intrinsic local identity that attracts and organizes particular input structure and specifies certain output. The development of the tangential and laminar specificity of thalamic projections to the cortex will be investigated in two experimental conditions. In the first experiment, a region of dorsal neocortex, principally visual cortex, will be removed in utero prior to the arrival of the first thalamic axons in the cortex, and the development, survival, mature projection pattern and volume of arbor of thalamic axons will be investigated. In the second manipulation, a developmental deletion of the layer IV and varying amounts of the supragranular layers will be made using a mitotic inhibitor, MAM (methylazoxymethanol acetate), with a parallel analysis. The intent of both of these manipulations is to delete the target population prior to any interaction of axon and target populations, and thus reveal any intrinsic specificity in the choice of cortical and laminar terminal area by incoming thalamocortical axons, and the mechanisms of population matching between the thalamus and cortex. The clinical significance of this work is direct: in addition to supplying basic information about the nature of cortical reorganization after brain damage, we will be directly describing what happens to the cortex after early local deletions, such as might happen with a vascular accident, or after a cytotoxic insult.