EARLY EVENTS IN CORTICAL DEVELOPMENT

丘脑皮质传入是感觉输入的唯一来源。 哺乳动物的大脑皮层。它们在大脑皮层发育过程中的作用 很重要。最近的研究证实，丘脑皮质的传入是 在建筑差异化的开发过程中需要， 连接和功能功能，区分和定义 成人新皮质中的功能化“区域”。四个 这项提案的具体目标旨在检验以下假设 被认为是控制特定地区发展的机制 丘脑皮质连接。这项工作将主要在老鼠身上进行， 是研究皮质发育和可塑性的极佳模型。它 将结合各种解剖学和细胞学方法，在体内使用 和体外实验方法，以及延时成像 培养的组织。主要的实验目标是： (1)评价丘脑皮质轴突靶向的特异性 以及它们对皮质板的入侵。 (2)研究假定的位置相关分子线索的作用 假设控制丘脑皮质轴突靶向的特异性。 (3)确定膜的成熟依赖变化是否- 皮质板层神经元和/或其表面的相关分子 可扩散的趋化物质的分泌促进了 皮质板由等待的丘脑皮质轴突组成。 (4)分析神经上皮细胞的弥散程度及其分布。 在新皮质前板发育过程中的后代作为一种手段 评价建立位置依赖关系的假想机制 子板块中的信息。 这项工作的长期目标是及早阐明关键问题 哺乳动物大脑皮层发育中的事件，重点是 在大脑皮层上。预计收集到的信息将 不仅提供对正常发育机制的洞察 大脑皮层，但它将有助于我们理解基础 在困扰人类的许多先天性皮质异常中， 作为后来的突发性神经退行性疾病。

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.