Tools for Analyzing Microcircuit Development of Ontogenetic Units in Mouse Cerebr
分析小鼠大脑个体发生单元微电路发育的工具
基本信息
- 批准号:7498811
- 负责人:
- 金额:$ 25.43万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2008
- 资助国家:美国
- 起止时间:2008-09-01 至 2010-05-31
- 项目状态:已结题
- 来源:
- 关键词:ArtsAutistic DisorderBehaviorBrainCell LineCellsCerebral cortexCognitionComplexDecision MakingDefectDevelopmentDrug abuseEmbryoEngineeringEpilepsyFacility Construction Funding CategoryFiberFluorescenceGoalsImage AnalysisImaging TechniquesIndividualLabelLeadLinkMapsMental RetardationMental disordersMorphogenesisMorphologyMothersMusNeural tubeNeuroepithelial CellsNeurogliaNeurologicNeuronsNumbersPerceptionPhysiologicalPlayPopulationPositioning AttributeProcessPropertyProteinsPublic HealthRadialResearchResolutionRestRetroviridaeRodentRoleStagingStem cellsStructureSurfaceSynapsesTechniquesTestingTissuesVertebral columnbasecomputerized toolsdaughter celldevelopmental neurobiologyin vivoinhibitory neuroninnovationinsightmalformationmigrationnerve stem cellneurogenesistool
项目摘要
DESCRIPTION (provided by applicant): An essential step towards understanding the function of a brain structure is to understand the intricacies of its neuronal interconnections. Extensive evidence suggests that neurons in the cerebral cortex are interconnected into functional columns. Moreover, columns with similar physiological properties are arranged close to each other and lead to the formation of cortical maps. At the level of neuronal populations, cortical maps varied smoothly across the surface of the cortex. However, recent studies demonstrate that neurons next to each in the cerebral cortex can have drastically different physiological properties, arguing that the microcircuit in functional columns is highly specific at the level of individual neurons. Given the daunting complexity in the number and type of neurons in the cerebral cortex, the formation of this fine-scale microcircuit is a seemingly bewildering task. This raises an intriguing possibility whether the formation of precise microcircuits in the cerebral cortex depends on the highly regulated processes underlying the early cortical development, e.g. neurogenesis and neuronal migration. It has been previously suggested that the formation of functional columns is related to ontogenetic radial units, the construction units of the cerebral cortex that consist of individual radial glial progenitor cells and associated daughter cells - migrating cortical neurons. To test this hypothesis, it is essential to identify ontogenetic radial units in the development cortex and investigate their morphological and functional development. In this project, we will develop new experimental and computational tools to label ontogenetic units of excitatory and inhibitory neurons in the developing cortex, analyze their morphological development, and map their synaptic connectivity. Specifically, we will engineer retroviruses that express fluorescence proteins and use them to infect dividing radial glial progenitor cells in the developing cortex in vivo in a cell/tissue specific manner. The morphogenesis of individual ontogenetic radial units expressing fluorescent proteins will be analyzed using state-of-the-art imaging techniques and powerful imaging analysis tools. Furthermore, we will combine whole-cell electrophysiological recordings with the latest development of photostimulation techniques to investigate the microcircuit development among neurons in ontogenetic units at single-cell resolution. The proposed research promises a wealth of new insights into the developmental and functional organization of the cerebral cortex. It will also facilitate the understanding and treatment of various neurological and psychiatric disorders caused by the cerebral cortex malformation and malfunction. PUBLIC HEALTH RELEVANCE This project will develop new experimental and computational tools for labeling neurons in the cerebral cortex that share the same origin and for investigating their morphological and functional development. It will advance and expand the understanding and treatment of a variety of neurological and psychiatric disorders caused through defects in cerebral cortex development and function, such as mental retardation, epilepsy, autism, and maladaptive decision-making behavior associated with drug abuse.
描述(由申请人提供):了解大脑结构功能的关键一步是了解其神经元相互连接的错综复杂。广泛的证据表明,大脑皮层中的神经元相互连接成功能柱。此外,具有相似生理特性的柱子彼此靠近地排列,并导致大脑皮层图谱的形成。在神经元群体的水平上,皮质地图在皮质表面上变化平稳。然而,最近的研究表明,大脑皮层中每个神经元旁边的神经元可能具有截然不同的生理特性,认为功能柱中的微电路在单个神经元水平上具有高度特异性。考虑到大脑皮层神经元的数量和类型令人望而生畏的复杂性,形成这种精细的微电路似乎是一项令人困惑的任务。这提出了一个耐人寻味的可能性,即大脑皮层精确微电路的形成是否依赖于支撑早期皮质发育的高度调控的过程,例如神经发生和神经元迁移。以前的研究表明,功能柱的形成与个体发育的放射状单位有关,放射状单位是大脑皮层的结构单位,由单个放射状胶质前体细胞和相关的子细胞-迁移的皮质神经元组成。为了验证这一假说,有必要确定发育皮质中的个体发育放射状单位,并研究它们的形态和功能发育。在这个项目中,我们将开发新的实验和计算工具来标记发育中的皮质中兴奋性和抑制性神经元的个体发生单位,分析它们的形态发育,并绘制它们的突触连接图。具体地说,我们将设计表达荧光蛋白的逆转录病毒,并使用它们以细胞/组织特异性的方式感染体内发育中的皮质中正在分裂的放射状神经胶质前体细胞。表达荧光蛋白的个体个体发育径向单位的形态发生将使用最先进的成像技术和强大的成像分析工具进行分析。此外,我们将结合全细胞电生理记录和光刺激技术的最新发展,在单细胞分辨率下研究个体发育单位神经元之间的微电路发育。这项拟议的研究有望为大脑皮层的发育和功能组织提供丰富的新见解。它还将促进对大脑皮层畸形和功能障碍引起的各种神经和精神疾病的了解和治疗。公共卫生相关性该项目将开发新的实验和计算工具,用于标记大脑皮层中具有相同来源的神经元,并研究它们的形态和功能发育。它将促进和扩大对大脑皮层发育和功能缺陷引起的各种神经和精神疾病的理解和治疗,如智力低下、癫痫、自闭症和与药物滥用有关的不良决策行为。
项目成果
期刊论文数量(0)
专著数量(0)
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Kun Huang其他文献
Kun Huang的其他文献
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{{ truncateString('Kun Huang', 18)}}的其他基金
Indiana Genomics Research Training Program for Data Scientists (INGEN4DS)
印第安纳州数据科学家基因组学研究培训计划 (INGEN4DS)
- 批准号:
10410773 - 财政年份:2022
- 资助金额:
$ 25.43万 - 项目类别:
Indiana Genomics Research Training Program for Data Scientists (INGEN4DS)
印第安纳州数据科学家基因组学研究培训计划 (INGEN4DS)
- 批准号:
10678920 - 财政年份:2022
- 资助金额:
$ 25.43万 - 项目类别:
Informatics Links Between Histological Features and Genetics in Cancer
癌症组织学特征与遗传学之间的信息学联系
- 批准号:
9070645 - 财政年份:2015
- 资助金额:
$ 25.43万 - 项目类别:
Informatics Links Between Histological Features and Genetics in Cancer
癌症组织学特征与遗传学之间的信息学联系
- 批准号:
9278131 - 财政年份:2015
- 资助金额:
$ 25.43万 - 项目类别:
Informatics Links Between Histological Features and Genetics in Cancer
癌症组织学特征与遗传学之间的信息学联系
- 批准号:
9675513 - 财政年份:2015
- 资助金额:
$ 25.43万 - 项目类别:
Tools for Analyzing Microcircuit Development of Ontogenetic Units in Mouse Cerebr
分析小鼠大脑个体发生单元微电路发育的工具
- 批准号:
7681070 - 财政年份:2008
- 资助金额:
$ 25.43万 - 项目类别:
MITF: Regulating Osteoclast Gene Expression and Function
MITF:调节破骨细胞基因表达和功能
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9015743 - 财政年份:1998
- 资助金额:
$ 25.43万 - 项目类别:
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