FOREBRAIN ORGANIZATION

描述(调查人员摘要)：申请者描述 发现一种新的大鼠品系，它具有不寻常的、遗传的 前脑异常。他们的行为和外貌 受影响的动物相对正常，但它们拥有“完全 新的大脑区域。最好的描述是一个大的皮质异位，新的 结构位于新皮质地幔下方，给出了总的 出现“双皮质”。突变区域是双侧的， 几乎延伸到整个大脑皮层的吻尾部 披风。这种老鼠品系的存在对两个人来说是令人兴奋的 相互重叠的原因。首先，它提供了测试的机会 关于结构和结构之间关系的各种理论 大脑皮层功能及其发育的基本规律 程序。第二，观测到的异常具有显著的 类似于一种被称为双皮质的人类疾病。 申请人提议研究这一新描述的异常现象。 有好几种方法。首先，申请者将进行描述性分析 异常中神经元的类型、位置和方向 成年突变动物的区域，以及对成分的任何影响 或覆盖在缺陷上的“正常”皮质的组织。第二, 申请人建议通过以下方式描述异位的发展 在几个发育年龄(期间)进行纵向研究 皮质醇生成)。这些研究将因决心而得到加强 异位的组成神经元的“生日”和 用BrdU掺入法覆盖幼鼠正常皮质 妊娠母鼠在不同胚胎和出生后早期注射 年龄后，在“成年”年龄献祭(P30-40)。脑室 异位神经元的来源及其迁移过程将是 使用短期存活的BrdU注射进行了研究。两到48小时后 BrdU管理到怀孕的大坝，她的幼崽将被带走， 评估标记细胞的位置。第三，内部连通性 异位以及异位与其他皮质和皮质下区域之间 将会被确定。将确定受影响区域的传入 通过将氟红宝石注射到三个吻部/尾部之一 在异常区域或上覆皮质内。的关注点 分析将针对其核与之相关的丘脑核团 上面的大脑皮层。异位症的不同之处将被确定 使用顺行示踪剂PHA-凝集素。这两个结果都将是 与来自上覆正常前脑的类似注射相比。 结果应该是对解剖学和 这种显着的遗传异常的发展。

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.