Cortical control over area-specific thalamic input

皮层对特定区域丘脑输入的控制

基本信息

批准号：
9300013
负责人：
ELIZABETH Elizabeth Grove
金额：
$ 8.08万
依托单位：
UNIVERSITY OF CHICAGO
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-03-01 至 2019-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9300013
关键词：
Affect Age Area Attention Axon Brain Brain Diseases Brain Injuries Cell Nucleus Cells Cerebral cortex Color Core Facility Cues Development Distant Embryo Face Fibroblast Growth Factor 8 Fluorescence Goals Growth Human Individual Injection of therapeutic agent Injury Label Laboratories Maps Mediating Memory Methods Microscope Molecular Movement Mus Natural regeneration Neocortex Outcome Perception Positioning Attribute Primordium Reporting Research Retina Rodent Route Sensory Signal Transduction Slice Stroke Structure Surface Testing Thalamic Nuclei Thalamic structure Time Tracer Transgenic Mice Travel Vibrissae Viral Vector Work barrel cortex base cortex mapping design developmental neurobiology digital experimental study morphogens neocortical nerve supply postnatal prevent somatosensory statistics transcription factor

Affect Age Area Attention Axon Brain Brain Diseases Brain Injuries Cell Nucleus Cells Cerebral cortex Color Core Facility Cues Development Distant Embryo Face Fibroblast Growth Factor 8 Fluorescence Goals Growth Human Individual Injection of therapeutic agent Injury Label Laboratories Maps Mediating Memory Methods Microscope Molecular Movement Mus Natural regeneration Neocortex Outcome Perception Positioning Attribute Primordium Reporting Research Retina Rodent Route Sensory Signal Transduction Slice Stroke Structure Surface Testing Thalamic Nuclei Thalamic structure Time Tracer Transgenic Mice Travel Vibrissae Viral Vector Work barrel cortex base cortex mapping design developmental neurobiology digital experimental study morphogens neocortical nerve supply postnatal prevent somatosensory statistics transcription factor

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项目摘要

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.

项目摘要/摘要感官丘脑核中继信息来自感官表面的信息，例如视网膜和颤音啮齿动物的脸与大脑皮层的脸，将皮质与外界联系起来。反过来主感觉新皮层项目的领域，以依次连接高阶新皮层区域，以介导这样的介导作为感知，记忆和运动控制的功能。知道直接的机制因此大脑功能的发展以及人脑疾病的基础异常发育的各个方面。尽管大量的研究发现了许多控制的细胞和分子信号丘脑轴突通过皮层结构的生长，以及如何精确分类轴突他们的路线很少关注皮质本身内的指导信号。却很大证据表明存在皮质内提示。拟议的工作将利用鼠标线来自感觉丘脑核的轴突已在遗传上用荧光标记。这会创建一个大脑表面的感觉区域的可见图。新皮层区域图将在这些小鼠通过操纵新皮质形态成纤维细胞生长因子8（FGF8），这将移动和重复的感觉区域。轴突示踪剂将放置在变化区域的不同部分地图，使用荧光图来识别所需的目标。示踪剂有时间旅行之后从皮层到丘脑，大脑将被固定和切片。标记的丘脑皮质的轨迹将使用共聚焦显微镜在3D中查看和重建轴突。这些轨迹会改变在皮质中正常丘脑指导的点上急剧，因为皮质图本身已经破坏了。该研究将检验以下假设：丘脑轴突的位置提示皮质子板和第4层（丘脑输入的主要接受者），将是研究此类提示的分子身份。