FOREBRAIN ORGANIZATION

前脑组织

• 批准号: 2037955
• 负责人: KEVIN Scott LEE
• 金额: $ 19.46万
• 依托单位: UNIVERSITY OF VIRGINIA
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-12-18 至 1998-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2037955
• 关键词: bromodeoxyuridine; cell migration; congenital brain disorder; developmental neurobiology; genetic strain; histology; intercellular connection; laboratory rat; neuroanatomy; neuronal transport; neurophysiology; prosencephalon

DESCRIPTION (Investigator's Abstract): The applicant describes the discovery of a new strain of rats that has an unusual, inherited forebrain abnormality. The behavior and external appearance of the affected animals are relatively normal, yet they possess an "entirely new brain region". Best described as a large cortical ectopia, the new structure is located below the neocortical mantle and gives the gross appearance of a 'double-cortex'. The mutant region is bilateral and extends for nearly the entire rostral-caudal extent of the cortical mantle. The existence of this rat strain is exciting for two overlapping reasons. The first is that it offers the opportunity to test a variety of theories about the relationship between structure and function in the cortex and about the ground rules of its developmental program. The second is that the anomaly observed bears a striking resemblance to a human condition known as double cortex. The applicant proposes to study this newly described abnormality in several ways. First, the applicant will perform a descriptive analysis of the types, positions and orientations of neurons in the anomalous region of adult mutant animals, as well as any effects on composition or organization of the "normal" cortex overlying the defect. Second, the applicant proposes to describe the development of the ectopia, by performing a longitudinal study at several developomental ages (during corticogenesis). These studies will be enhanced by the determination of the "birthdays" of the constituent neurons of the ectopia and the overlying normal cortex using BrdU incorporation into pups after injection of the pregnant dams at various embryonic and early postnatal ages followed by sacrifice at "adult" ages (P30 - 40). The ventricular source of the ectopic neurons and the course of their migration will be studied using short survival BrdU injections. Two to 48 hours after BrdU administration to a pregnant dam, her pups will be taken and the location of the labeled cells assessed. Third, connectivity within the ectopia and between the ectopia and other cortical and subcortical areas will be determined. Afferents to the affected region will be determined by injections of Fluoro ruby into one of three rostro/caudal sites within the anomalous region or the overlying cortex. The focus of analysis will be on the thalamic nuclei whose nuclei are associated with the overlying cortex. Efferents from the ectopia will be determined using the anterograde tracer PHA-lectin. Both of these results will be compared with similar injections from the overlying normal forebrain. The result should be a comprehensive description of the anatomy and development of this remarkable genetic anomaly.

描述（研究者的摘要）：申请人描述 发现具有不寻常的，继承的新老鼠菌株 前脑异常。行为和外观 受影响的动物相对正常，但它们具有“完全 新的大脑区域”。最佳描述为一个大型皮质骨质，新的 结构位于新皮层地幔下方，并给出总的 “双层皮质”的外观。突变区是双侧的， 延伸几乎整个皮质的尾声范围 地幔。对于两个人来说，这种老鼠菌株的存在令人兴奋 重叠的原因。首先是它提供了测试的机会 关于结构与结构之间关系的各种理论 在皮层中的功能以及其发展的基本规则 程序。第二个是异常观察到了惊人的 与人类状况相似，称为双层皮质。 申请人建议研究这种新描述的异常 几种方式。首先，申请人将执行描述性分析 神经元异常的类型，位置和方向 成年突变动物的区域，以及对组成的任何影响 或组织上覆盖缺陷的“正常”皮层的组织。第二， 申请人提议描述外骨的发展， 在几个发展年龄进行纵向研究（在 皮质发生）。这些研究将通过确定来增强 ectopia和 将正常皮质覆盖在幼崽中使用BRDU掺入后的正常皮质 在各种胚胎和早期产后注射怀孕的大坝 年龄随后在“成人”年龄牺牲（P30-40）。心室 异位神经元的来源及其迁移过程将是 使用短生存的BRDU注射研究。两到48小时后 BRDU管理到怀孕的大坝，将服用她的幼犬 评估标记的细胞的位置。第三，连通性 外生以及外交和其他皮质和皮层下区域之间 将确定。将确定受影响地区的传入 通过注射Fluoro Ruby进入三个Rostro/Caudal位点之一 在异常区域或上覆的皮层内。重点 分析将在丘脑核上，其核与 上覆的皮层。将确定来自外交的侵害。 使用顺行示踪剂PHA骨蛋白。这两个结果将是 与上面正常前脑的相似注射相比。 结果应该是对解剖结构和 这种显着的遗传异常的发展。