EARLY EVENTS IN CORTICAL DEVELOPMENT

丘脑皮层传入神经是感觉输入的唯一来源， 哺乳动物新皮层它们在皮层发育过程中的作用 重要.最近的工作已经确定，丘脑皮层传入神经是 在开发过程中需要区分建筑， 连接和功能特征，区分和定义 成年人大脑新皮层中功能专门化的“区域”。 四 该提案的具体目标是检验以下假设： 控制特定区域发展的机制 丘脑皮质连接 这项工作将主要在大鼠中进行， 是研究皮质发育和可塑性的极好模型。 它 将联合收割机结合各种解剖学和细胞学方法， 和体外实验方法，以及时间推移成像， 培养组织主要的实验目标是： (1)评估丘脑皮质轴突靶向的特异性 以及它们对皮质板的侵犯 (2)来研究假定的位置依赖性分子线索 假设控制丘脑皮质轴突靶向的特异性。 (3)以确定膜的成熟依赖性变化- 皮质板神经元和/或它们的细胞表面上的缔合分子 可扩散的化学引诱物的分泌促进了 皮质板通过等待丘脑皮质轴突。 (4)分析神经上皮细胞的分散程度及其 作为一种手段， 评估建立位置依赖的假设机制 在subplate的信息。 这项工作的长期目标是阐明关键的早期 哺乳动物大脑皮层发育过程中的事件， 在大脑皮层上。预计收集到的信息将 不仅提供了对正常发育机制的见解， 大脑皮层，但它将有助于我们理解 许多折磨人类的先天性皮层异常， 神经退行性疾病。

Thalamocortical afferents are the sole source of sensory input to the mammalian neocortex. Their role during cortical development is equally important. Recent work has established that thalamocortical afferents are required during development for the differentiation of the architectural, connectional and functional features that distinguish and define the functionally specialized "areas" in the adult neocortex. The four specific aims of this proposal are designed to test hypotheses on mechanisms postulated to control the development of area-specific thalamocortical connections. This work will be done principally in rats, an excellent model for studies of cortical development and plasticity. It will combine a variety of anatomical and cellular methods, using in vivo and in vitro experimental approaches, as well as time-lapse imaging of cultured tissue. The major experimental goals are: (1) to assess the specificity in the targeting of thalamocortical axons and their invasion of the cortical plate. (2) to investigate a role for putative position-dependent molecular cues hypothesized to control specificity in thalamocortical axon targeting. (3) to determine whether maturation-dependent changes in membrane- associate molecules on the surfaces of cortical plate neurons and/or their secretion of a diffusible chemoattractant promotes the invasion of the cortical plate by waiting thalamocortical axons. (4) to analyze the degree of dispersion of neuroepithelial cells and their progeny during the development of the neocortical preplate as a means to evaluate hypothesized mechanisms of establishing position-dependent information in the subplate. The long term objectives of this work are to elucidate critical early events in the development of the mammalian cerebral cortex, with a focus on the neocortex. It is expected that the information gathered will provide insights not only into normal developmental mechanisms employed in the cortex, but that it will contribute to our understanding of the basis of the many congenital cortical abnormalities that afflict humans, as well as later striking neurodegenerative diseases.