DEVELOPMENT OF LOCAL CONNECTIONS IN CEREBRAL CORTEX

大脑皮层局部连接的发展

• 批准号: 6302716
• 负责人: Susan K McConnell
• 金额: $ 23.78万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-12-01 至 2000-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6302716
• 关键词: axon; brain electrical activity; developmental neurobiology; epilepsy; fluorescent dye /probe; growth cones; laboratory rat; neocortex; neuronal guidance; organ culture; pyramidal cells; visual cortex

During development, young neurons within the nervous system must form specific connections to both local and long distance targets. Within the cerebral cortex, the majority of synaptic connections are formed by locally-projecting neurons; thus it seems likely that the malformation of such connections will be implicated in the generation of at least some of the epilepsies of childhood. Indeed, use of high resolution MRI has made it increasingly apparent that a number of the epilepsies are caused b cortical malformations. We need to understand much more about the rules by which connections form in the normal cortex, in order to understand and possibly treat the defects within cortical malformations that lead to epilepsy. The rules by which local connections are established during development appear to employ highly specific mechanisms of laminar recognition. The major aim of this research proposal is to understand the processes by which young neurons in the mammalian neocortex form local (intrinsic) axonal connections with appropriate sets of target neurons in restricted sets of layers. We will explore the development of the local projections of neurons the cells of cortical layer 2/3, which form extensive interconnections within layer 2/3 and also project to the deep layers 5 and 6; those of neurons in layer 5, which projects up to layer 2/3 and to the deep layers; and finally those of the cortical layer 6, which sends a feedback projection to layer 4. The following specific aims are outlined: 1) We will use organotypic cultured slices of the developing visual cortex to ask whether local circuit formation be recapitulated in slices, and whether axons require activity to establish their layer-specific patterns of axon collaterals. 2) By placing neurons in ectopic laminar positions, we will ask whether the formation of local projections an active process that involves the specific recognition of layer-specific cues. 3) Using membrane stripe assays in which neurons of the different layers are presented with a choice of growth substrates, we will explore the nature of the molecular cues that direct local axonal growth and sprouting in the cortex.

在发育过程中，神经系统内的年轻神经元 必须与本地和长途形成特定的连接 目标的 在大脑皮层中，大多数突触 连接是由局部投射神经元形成的;因此， 这种连接的畸形很可能与 至少是一些儿童癫痫的发生。 事实上，高分辨率MRI的使用已经使其越来越多地 很明显，许多癫痫是由B皮层引起的， 畸形 我们需要更多地了解规则 通过这种连接在正常皮质中形成，以便 了解并可能治疗皮质内的缺陷， 导致癫痫的畸形 当地的规则 在开发过程中建立的连接似乎采用了 高度特异性的层流识别机制 主要目标 这项研究的目的是了解 哺乳动物新皮层中的年轻神经元形成局部（内在） 轴突与适当的靶神经元的连接， 层的限制集。 我们会探讨如何发展 神经元的局部投射是皮质2/3层的细胞， 在第2/3层内形成广泛的互连， 到深层5和6;那些在第5层的神经元， 投影到2/3层和深层;最后， 皮质层6向层4发送反馈投影。 具体目标如下：（1）我们将使用 发育中的视觉皮层的器官型培养切片， 局部电路的形成是否以切片形式概括，以及 轴突是否需要活动来建立它们的层特异性 轴突侧支的模式。2)通过将神经元放置在 层流位置，我们会问是否形成局部 预测一个积极的过程，涉及具体的认识， 特定于层的线索。 3)使用膜条纹测定，其中 不同层的神经元具有以下选择： 生长基质，我们将探索分子线索的性质 指导局部轴突生长和皮层发芽。