Identification of Core Pathways that Regulate Dendrite Morphology

调节树突形态的核心途径的识别

• 批准号: 0548543
• 负责人: Bonnie Firestein
• 金额: $ 36万
• 依托单位: Rutgers University New Brunswick
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-01 至 2009-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0548543&HistoricalAwards=false
• 关键词: Identification; Core; Pathways; Regulate; Dendrite

Firestein - Identification of Core Pathways that Regulate Dendrite MorphologyProposal 0548543Abstract In order for proper neuronal function to occur, the neuron must have the correct number of input centers, or dendrites, which look like branches on a tree. However, very little is currently known about how the pattern of these branches is determined. The goal of Dr. Firestein's work is to identify core pathways by which dendrite number is regulated. Dr. Firestein will make use of molecular biology, biochemistry, and neuronal cell culture to investigate these pathways. First, Dr. Firestein will establish four criteria by which to characterize regulators of dendrite number. This system, not unlike criteria used to characterize neurotransmitters, will help to identify whether proteins reported in the literature are indeed members of core pathways for dendrite branching. Experiments will focus on two proteins, cypin and PSD-95, which Dr. Firestein believes to be components of the core pathway. Since the cytoskeleton, or supporting structure of a dendrite, must change when a dendrite branches, experiments will assess whether cypin and PSD-95 change dendrite number by altering the cytoskeleton. Second, the proposed studies will be extended to assess the role of other presumed proteins in the core program of dendrite branching. Other proteins will be tested to see if they they act together with cypin and PSD-95 by using cultured hippocampal neurons that have altered levels of these proteins. Finally, Dr. Firestein's group will take images of cultured hippocampal neurons over time using both static pictures and video microscopy and identify how dendrites form: via outgrowth, sprouting, or retraction. These studies are important because they will provide information on how dendrite branching is regulated during development to yield a functional brain. The impact of this research is far-reaching. The performance of the experiments will be part of a program to train undergraduate and graduate students in cutting-edge techniques in neuroscience and in practical aspects of experimental design and data interpretation. Furthermore, Dr. Firestein continues to mentor teachers on sabbatical from high school. By exposing high school teachers and students to experimental biology, the proposed research will motivate future scientists at a very early stage in their careers.

Firestein-识别调节树突形态的核心途径建议0548543为了正常的神经元功能，神经元必须有正确数量的输入中心或树突，它们看起来像树上的分支。然而，目前对这些分支的模式是如何确定的知之甚少。费尔斯坦博士的工作目标是确定调控树突数量的核心途径。费尔斯坦博士将利用分子生物学、生物化学和神经细胞培养来研究这些途径。首先，费尔斯坦博士将建立四个标准来描述树突数量的调控因素。这个系统与用来表征神经递质的标准没有什么不同，它将有助于确定文献中报道的蛋白质是否确实是树突分支的核心途径的成员。实验将聚焦于两种蛋白质，cypin和PSD-95，费尔斯坦博士认为这两种蛋白质是核心通路的组成部分。由于树突的细胞骨架或支撑结构在树突分支时必须改变，因此实验将评估Cypin和PSD-95是否通过改变细胞骨架来改变树突数量。其次，拟议的研究将扩展到评估其他假定蛋白质在树突分支的核心计划中的作用。其他蛋白质将通过使用培养的改变这些蛋白质水平的海马神经元进行测试，以确定它们是否与cypin和PSD-95一起作用。最后，费尔斯坦博士的团队将使用静态图片和视频显微镜拍摄培养的海马神经元随时间推移的图像，并确定树突是如何形成的：通过长出、发芽或收缩。这些研究很重要，因为它们将提供关于树突分支在发育过程中如何调节以产生功能大脑的信息。这项研究的影响是深远的。这些实验的表现将是培训本科生和研究生神经科学尖端技术以及实验设计和数据解释实用方面的计划的一部分。此外，费尔斯坦博士还继续指导高中放假的教师。通过让高中教师和学生接触实验生物学，拟议的研究将激励未来的科学家在他们职业生涯的非常早期阶段。