Brain Cytoarchitectonic Characterization of Williams Syndrome

我们要求继续支持研究威廉姆斯I综合征（WS）中基因和行为之间的解剖学联系。目前的研究阶段将继续完善的假设，已经出现了从综合的集体结果，从前一个时期的项目I-V的总体假设，从神经认知，解剖和成像，神经生理学，andl遗传研究结果在WS暗示了一个无序的建立在大脑皮层的形成过程中的背腹和前后梯度。具体的假设是，背侧尾侧皮层的建立和功能异常是一些缺失基因的直接结果，腹侧和前皮质 到目前为止，解剖学研究表明背侧中央沟缩短，背尾侧前脑减少。在结构水平上，细胞测量表明背侧和腹侧后皮质都有改变，但类型不同，这与神经影像学结果一致，显示尾背侧区缩短，额叶和腹侧区相对扩大。一个独特的部分缺失的情况下，我们研究转录因子GTF 21和GTF 21 rd染色的视觉皮层，这表明异常的皮层相关的背侧视觉通路。 本项目的这一部分的具体目标与总体假设有关：因此，我们将比较尾部和前部的背侧和腹侧皮质。一个推论假说声称，背尾侧脑的异常意味着除了空间视觉皮层之外，其他空间相关的皮层也会被发现异常。第二个推论是，WS的异常亲和行为与腹前区的增强发育有关，包括杏仁核，外侧下丘脑和相关的前内侧皮层，这也将是本研究的目的之一。最后，两个皮质下核，LGN和MGN将进行研究的假设，这些核内的magnocellular子系统与差异的背尾侧和腹尾侧皮质。拟议研究的一个主要目的是提供信息，为在行为， 神经生理学，成像和遗传组件的程序项目，以及从这些项目中的发现得出的线索，以帮助指导我们的研究在本项目。迄今为止，这种合作的成效大于各部分的总和。

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.