Cortical control over area-specific thalamic input

项目摘要/摘要 丘脑感觉核传递来自感觉表面的信息，如视网膜和触须。 啮齿动物的脸连接到大脑皮层，连接大脑皮层和外部世界。反过来，初级感官 新皮质投射到顺序连接的高级新皮质区域，这些区域介导了 起到感知、记忆和运动控制的作用。知道引导人们 因此，丘脑皮质轴突到正确的新皮质靶点对于理解 大脑功能的发展，以及人类大脑疾病潜在的异常发育的方面。 尽管大量的研究已经发现了许多控制细胞和分子信号的 丘脑轴突通过皮质下结构的生长，以及轴突是如何精确分类的 在他们的路线上，很少有人关注大脑皮层内部的引导信号。然而，数量很大 有证据表明，皮质内线索是存在的。拟议中的工作将利用一种鼠标线，其中 来自丘脑感觉核团的轴突已经被基因标记为荧光。这将创建一个 大脑表面感觉区域的可见地图。新大脑皮层区域地图将在 通过操纵新皮质形态生成物成纤维细胞生长因子8(FGF8)，这些小鼠将 移动和复制感觉区域。轴突示踪剂将放置在改变的区域的不同部分 地图，使用荧光地图来识别所需的目标。在示踪剂有时间旅行之后 从大脑皮质到丘脑，大脑将被固定和切片。标记丘脑皮质的运动轨迹 轴突将使用共聚焦显微镜进行3D观察和重建。这些轨迹将会改变 大脑皮质中的正常丘脑引导点发生戏剧性的变化，因为皮质地图本身 打乱了。这项研究将检验这样一种假设，即丘脑轴突的位置线索存在于 皮质亚板和在第四层，丘脑输入的主要接受者，并将作为 研究这类线索的分子同一性。

PROJECT SUMMARY/ABSTRACT Sensory thalamic nuclei relay information from sensory surfaces such as the retina and the vibrissae on rodent's face to the cerebral cortex, connecting the cortex with the outside world. In turn primary sensory areas of neocortex project to sequentially connected higher order neocortical areas that mediate such functions as perception, memory and movement control. Knowing the mechanisms that direct thalamocortical axons to the correct neocortical target is therefore important for understanding the development of brain function, and aspects of abnormal development underlying human brain disorders. Although an abundance of studies has uncovered many cellular and molecular signals that control the growth of thalamic axons through subcortical structures, as well as how axons are precisely sorted along their route, little attention has been paid to guidance signals inside the cortex itself. Yet substantial evidence indicates that intra-cortical cues exist. The proposed work will utilize a mouse line in which axons from sensory thalamic nuclei have been genetically labeled with fluorescence. This creates a visible map of sensory areas on the surface of the brain. The neocortical area map will be altered in these mice by manipulating the neocortical morphogen Fibroblast Growth Factor 8 (FGF8), which will shift and duplicate sensory areas. Axonal tracers will be placed in different parts of the altered area map, using the fluorescent map to identify the desired targets. After the tracer has had time to travel from cortex to thalamus, the brain will be fixed and sectioned. The trajectories of labeled thalamocortical axons will be viewed and reconstructed in 3D using a confocal microscope. These trajectories will shift dramatically at points of normal thalamic guidance in the cortex because the cortical map itself has been disrupted. The study will test the hypothesis that positional cues for thalamic axons are present in the cortical subplate and in layer 4, the major recipient of thalamic input, and will be a preface to investigating the molecular identity of such cues.