FOREBRAIN ORGANIZATION

前脑组织

• 批准号: 2609682
• 负责人: KEVIN Scott LEE
• 金额: $ 20.23万
• 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/2609682
• 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（研究者摘要）：申请人描述了 发现了一种新的老鼠品系， 前脑异常的行为和外观 受影响的动物是相对正常的，但他们拥有一个“完全”， 新的大脑区域”。最好的描述是一个大的皮质异位，新的 结构位于新皮层地幔下方，并给出了总的 出现了“双皮质”。突变区域是双侧的， 几乎延伸到皮质的整个头尾部范围 地幔这种老鼠品系的存在令人兴奋， 重叠的原因。第一，它提供了一个检验 各种关于结构和 功能及其发展的基本规则 程序.第二，观察到的异常现象具有惊人的 类似于人类的双重大脑皮层 申请人建议研究这种新描述的异常， 几种方式。首先，申请人将进行描述性分析 异常脑区神经元的类型、位置和方向 成年突变动物的区域，以及对组成的任何影响 或覆盖缺损的“正常”皮质的组织。第二、 申请人提出通过以下方式描述异位的发展： 在几个发育年龄进行纵向研究（在 皮质生成）。这些研究将得到加强， 异位神经元的“生日”， 使用BrdU掺入到幼鼠中覆盖正常皮质， 在不同的胚胎和出生后早期注射妊娠母鼠 年龄，然后在“成年”年龄（P30 - 40）处死。心室 异位神经元的来源及其迁移过程将是 使用短期存活的BrdU注射进行研究。两到四十八小时后 对怀孕的母鼠进行BrdU给药，将取下她的幼崽， 评估标记细胞的位置。第三，互联互通 异位和异位与其他皮质和皮质下区域之间 将被确定。将确定受影响区域的传入 通过将Fluoro ruby注射到三个喙/尾部位之一 在异常区域或覆盖的皮层中。的焦点 分析将在丘脑核，其核与 覆盖的皮层异位的传出物将被确定 使用顺行示踪PHA-凝集素。这两个结果将是 与来自覆盖正常前脑的类似注射相比。 结果应该是对解剖结构的全面描述， 这一显著的遗传异常的发展。