Brain Cytoarchitectonic Characterization of Williams Syndrome

威廉姆斯综合征的脑细胞结构特征

• 批准号: 7003885
• 负责人: ALBERT Mark GALABURDA
• 金额: $ 15.91万
• 依托单位: SALK INSTITUTE FOR BIOLOGICAL STUDIES
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-04-05 至 2009-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7003885
• 关键词: Williams syndrome; adolescence (12-20); behavioral /social science research tag; behavioral genetics; brain morphology; cell morphology; cerebral cortex; developmental genetics; developmental neurobiology; gene deletion mutation; human subject; neurogenetics; patient oriented research; transcription factor; young adult human (21-34)

We are requesting continuing support to study anatomical links between genes and behavior in Williams I Syndrome (WS). The present period of research will continue to refine the testing of hypotheses that have emerged from the synthesis of collective results from the previous period across Projects I-V. The overarching hypothesis stemming from the neurocognitive, anatomical and imaging, neurophysiological, andl genetic findings in WS implicates a disordered establishment of dorsoventral and anteroposterior gradients during the formation of cerebral cortex. The specific hypothesis is that the dorsal caudal cortex is set up and functions abnormally as a direct result of some of the deleted genes, and that ventral and anterior cortices change anatomically and functionally because of it. Thus far anatomical research showed curtailment of the dorsal central sulcus and reduction in dorsocaudal forebrain. At the architectonic level, cell measurements indicated alterations both in dorsal and ventral posterior cortices, but of different types, which is congruenl with neuroimaging results showing curtailement of caudodorsal areas and relative enlargement of frontal and ventral areas. A unique partial deletion case led us to study transcription factors GTF21 and GTF21rd staining in visual cortex, which showed abnormalities in cortex related to the dorsal visual pathway. The specific aims of this component of the Program Project relate to the overarching hypothesis: Thus, we will compare dorsal and ventral cortices caudally and frontally. A corollary hypothesis claims that abnormalities in dorsocaudal brain means that other spatially related cortices, in addition to the spatial visual cortex, will be found to be abnormal. A second corollary is that the abnormal affiliative behavior in WS is related to enhanced development of ventral anterior regions, including the amygdala, the lateral hypothalamus, and relevant frontomedial cortex, which will be one aim in this study, too. Finally, two subcortical nuclei, the LGN and the MGN will be studied with respect to the hypothesis that magnocellular subsystems within these nuclei relate differentially to the dorsocaudal and ventrocaudal cortex. A major aim of the proposed research will be to provide information that will inform research carried out in the behavioral, neurophysiological, imaging, and genetic components of the program project, as well as deriving clues from findings in those project to help guide our research in the present project. The collaboration, thus far, has been productive to a greater degree than the sum of its parts.

我们请求继续支持研究威廉姆斯 I 综合征 (WS) 基因与行为之间的解剖学联系。本期研究将继续完善对前一期项目 I-V 集体结果综合得出的假设的检验。源于 WS 的神经认知、解剖和成像、神经生理学和遗传学发现的总体假设表明，大脑皮层形成过程中背腹侧和前后梯度的建立无序。具体的假设是，背侧尾侧皮质的建立和功能异常是一些缺失基因的直接结果，而腹侧和前侧皮质 因此在解剖学和功能上发生变化。迄今为止，解剖学研究表明背侧中央沟缩小，背尾前脑缩小。在结构水平上，细胞测量表明背侧和腹侧后皮质均发生变化，但类型不同，这与神经影像学结果一致，显示尾背区域减少，额侧和腹侧区域相对扩大。一个独特的部分缺失案例使我们研究了视觉皮层中的转录因子 GTF21 和 GTF21rd 染色，这显示了与背侧视觉通路相关的皮层异常。 该计划项目这一部分的具体目标与总体假设相关：因此，我们将从尾部和正面比较背侧和腹侧皮质。一个推论假设声称，背尾脑的异常意味着除了空间视觉皮层之外的其他空间相关皮层也会被发现异常。第二个推论是，WS 中异常的亲和行为与​​腹侧前部区域的增强发育有关，包括杏仁核、外侧下丘脑和相关的额内侧皮层，这也将是本研究的目标之一。最后，将根据以下假设来研究两个皮质下核，即 LGN 和 MGN，这些核内的大细胞子系统与背尾皮质和腹尾皮质存在差异相关。拟议研究的一个主要目的是提供信息，为在行为、 该项目的神经生理学、成像和遗传组成部分，以及从这些项目的发现中得出线索，以帮助指导我们在当前项目中的研究。迄今为止，这种合作的成效远大于各个部分的总和。