NEURON DEATH IN CENTRAL NERVOUS SYSTEM DEVELOPMENT

新皮质是一种基本均匀的层状结构。 在细胞组成上有地区性差异 连通性。细胞内的主要区域变异 正常新皮质的组成是存在的和相对的 丘脑主要靶点--颗粒层IV的发育 传入，由各种类型的星状细胞和其他细胞组成 非锥体细胞。在实验操作中 在发育过程中，正常的颗粒状皮质可以变得无颗粒 由丘脑早期损伤引起。有趣的是，校长 唐氏综合征患者大脑皮质细胞构筑异常 此外，也没有第IV层和颗粒细胞，特别是 棘状星状细胞。因此，第四层的大小和组成 显示正常大脑皮质和大脑皮质的显著变异性 病理上的可变性，并且可以通过实验进行操纵。 我们建议研究其发育机制 在大脑皮层产生这些正常和不正常的变化 各种神经解剖学技术。 通过标记在特定胚胎上生成的新皮质细胞 使用氚胸腺嘧啶核苷的天数，以及它们的数量和 在皮质中的分布到成熟，通常在 第IV层的相对大小，以及丘脑早期以后的皮质 损伤，我们将调查细胞的正常贡献 产生和细胞死亡的这一特征的皮质变异性。 氚胸腺嘧啶核苷标记推定IV层的应用 结合其他细胞识别技术， 包括高尔基染色，逆行运输的HRP， 荧光示踪剂和免疫组织化学将使我们能够 确定细胞身份的哪些特征可能会正常变化，以及 试验性的。最终，我们将确定哪些功能 新皮质细胞的身份固定在世代上，并且 要素是在早期通过细胞交互指定或选择的 发展。这些结果将直接影响到 对新皮质病理发育的理解， 尤其是围产期创伤引起的脑性瘫痪和 唐氏综合症。

The neocortex is a structure of fundamentally uniform lamination that has regional variations in cellular composition and connectivity. The major regional variation in the cellular composition of the normal neocortex is the presence and relative development of a granular Layer IV, principal target of thalamic afference, composed of various types of stellate cells and other nonpyramidal cells. In experimental manipulations of development, a normally granular cortex can be made agranular by early thalamic lesions. Interestingly, the principal cytoarchitectonic abnormality of the cortex in Down syndrome is also the absence of Layer IV and granule cells, specifically aspinous stellate cells. Thus, the size and composition of Layer IV shows both substantial variability in the normal cortex and variability in pathology, and can be manipulated experimentally. We propose to investigate the developmental mechanisms which produce these normal and abnormal variations in the cortex using a variety of neuroanatomical techniques. By labelling neocortical cells generated on a particular embryonic days with tritiated thymidine, and following their number and distribution to maturity in cortices which normally vary in the relative size of Layer IV, and in cortices after early thalamic lesions, we will investigate the normal contribution of cell generation and cell death to this feature of cortical variability. The use of tritiated thymidine labelling of presumptive Layer IV cells in combination with other cell identification techniques, including Golgi staining, retrogradely transported HRP, fluorescent tracers and immunohistochemistry will allow us to determine which features of cell identity may vary normally and experimentally. Eventually, we will determine which features of neocortical cell identity are fixed on generation, and which features are specified or selected by cellular interactions in early development. These results will have direct implications for the understanding of pathological development of the neocortex, particularly cerebral palsy consequent to perinatal trauma and Down syndrome.