FORMATION OF THE VISUAL CORTEX

视觉皮层的形成

• 批准号: 3465938
• 负责人: JANICE Rae NAEGELE
• 金额: $ 10.03万
• 依托单位: WESLEYAN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-08-01 至 1997-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3465938
• 关键词: biomarker; brain mapping; cell cell interaction; cell death; cytotoxicity; developmental neurobiology; experimental brain lesion; fluorescent dye /probe; growth factor receptors; immunocytochemistry; immunologic assay /test; laboratory mouse; laboratory rat; microscopy; monoclonal antibody; neuroanatomy; neurotrophic factors; visual cortex; western blottings

The cellular and molecular substrates associated with the death of massive numbers of neurons in the developing visual system remain poorly characterized. One of the more distinctive neuronal populations to undergo developmental cell death is found in the subplate zone, a transient layer of the immature cerebral cortex. This population differentiates into a number of neurochemically and morphologically distinct types which form the initial intra-cortical and subcortical projections of the visual cortex and receive the first functional synaptic contacts from the dorsal lateral geniculate nucleus. Although the formation and the elimination of the subplate and its connections are likely to be of major biological significance for understanding mechanisms of cortical development, the events controlling cell death in this neuronal population are largely unknown. The first objective of the proposed studies is to provide a detailed description of the cellular and molecular interactions between the subplate neurons and geniculocortical and corticocortical axons before and during the period of cell death, using subplate-specific molecular markers and antisera against neurotrophic factors and receptors, in conjunction with anatomical techniques at the light- and electron microscopic levels. The second objective is to biochemically characterize a newly-identified antigen (SP1) expressed by the subplate cells during the period of cell death and its regulation, using monoclonal antibodies, in combination with biochemical approaches. The third objective is to define the types of cell death in the subplate. This objective will be achieved by comparing molecular properties of neurons undergoing naturally-occurring versus experimentally-induced cell death. These studies will further our understanding of the role of the subplate in formation of the visual cortex and the causes of cell death in this structure. They represent important first steps in identifying the early and specific markers for cell death in both normal development and in genetic mutations. The new information gained could also provide a rational strategy for the discovery of clinical interventions to prevent vision loss associated with acute conditions causing neuronal degeneration, such as ischemia, stroke and trauma.

与大量死亡相关的细胞和分子底物 发育中的视觉系统中的神经元数量仍然很少 特点。 比较独特的神经元群体之一 发育细胞死亡发生在板下区域，这是一个过渡层 不成熟的大脑皮层。 该群体分化为 形成神经化学和形态学上不同类型的数量 视觉皮层的初始皮层内和皮层下投影 接收来自背外侧的第一个功能性突触接触 膝状核。 虽然形成和消除 底板及其连接可能具有重要的生物意义 对于理解皮质发育机制具有重要意义 控制该神经元群中细胞死亡的事件很大程度上是 未知。 拟议研究的首要目标是提供 详细描述了细胞和分子之间的相互作用 之前和之前的板下神经元以及膝皮质和皮质皮质轴突 在细胞死亡期间，使用亚板特异性分子标记 和抗神经营养因子和受体的抗血清，联合使用 利用光学和电子显微镜水平的解剖技术。 第二个目标是对新鉴定的生物化学特征进行表征 细胞时期亚板细胞表达的抗原（SP1） 死亡及其调节，使用单克隆抗体，结合 生化方法。 第三个目标是定义细胞类型 死亡于底板。 这一目标将通过比较来实现 神经元的分子特性经历自然发生与 实验诱导的细胞死亡。 这些研究将进一步推动我们 了解亚板在视觉皮层形成中的作用 以及该结构中细胞死亡的原因。 他们代表着重要的 识别细胞死亡的早期和特异性标记物的第一步 正常发育和基因突变。 新信息 所得结果还可以为临床发现提供合理的策略 预防与急性病症相关的视力丧失的干预措施 引起神经元变性，例如缺血、中风和创伤。