NEURON DEATH IN CENTRAL NERVOUS SYSTEM DEVELOPMENT

新皮层是一种基本上均匀分层的结构 在细胞组成上有区域差异， 连通性。细胞中的主要区域变化 正常新皮层的组成是存在和相对 颗粒层IV的发展，丘脑的主要目标 传入，由各种类型的星状细胞和其他 非锥体细胞 在实验操作中， 在发育过程中，一个正常的颗粒状皮质可以变成无颗粒的 早期丘脑病变 有趣的是，校长 唐氏综合征患者大脑皮层的细胞结构异常， 也缺乏IV层和颗粒细胞，特别是 棘状星状细胞 因此，层IV的尺寸和组成 显示了正常皮层的实质性变化， 病理学的可变性，并且可以通过实验来操纵。 我们建议调查的发展机制， 在大脑皮层中产生这些正常和异常的变化， 各种神经解剖学技术 通过标记在特定胚胎上产生的新皮层细胞， 天与氚化胸苷，并按照其数量和 分布到成熟的皮质，通常在不同的 第四层的相对大小，以及丘脑早期后的皮质 病变，我们将研究细胞的正常贡献 代和细胞死亡的皮质变异性的这一特点。 使用氚化胸苷标记推定的第IV层 细胞与其它细胞识别技术相结合， 包括高尔基体染色，逆行转运HRP， 荧光示踪剂和免疫组织化学将使我们能够 确定小区标识的哪些特征可以正常变化， 实验性的 最终，我们将确定哪些特征 新皮层细胞的身份是固定的代， 特征是由早期的细胞相互作用指定或选择的。 发展 这些结果将直接影响到 了解新皮层的病理发展， 特别是由于围产期创伤引起的脑瘫， 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.