Searching for Connectivity Principles in the Brain

寻找大脑中的连接原理

• 批准号: 7089835
• 负责人: ARMEN STEPANYANTS
• 金额: $ 12.2万
• 依托单位: NORTHEASTERN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-07-01 至 2009-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7089835
• 关键词: axon; cell morphology; computational neuroscience; dendrites; developmental neurobiology; gamma aminobutyrate; interneurons; neocortex; neural plasticity; neurogenesis; neuronal guidance; neurons; neuropil; pyramidal cells; synapses; three dimensional imaging /topography; training

DESCRIPTION (provided by applicant): Understanding synaptic connectivity principles in the local circuits of mammalian brains is one of the oldest and most important problems in neuroscience. Without clear knowledge of connectivity principles it is virtually impossible to understand how the brain functions or to understand neural circuitry changes, which underlie neurological disorders. The morphology of neuronal arbors holds valuable information about the principles of synaptic connectivity in the brain. Quantitative analysis of neuronal morphology can shed light on a number of important questions: Are there precise wiring mechanisms during development that lead to specific connectivity patterns in the adult brain? What are the structural plasticity potentials for connectivity between different classes of neurons? What are the strategies used by different neuronal classes to find their post-synaptic partners? We are developing a consistent methodology, which will put us in a position to approach these questions in a quantitative manner. We are building a new method for detecting significant spatial correlations between pairs of neuronal arbors reconstructed in three dimensions (3D). This method has potential for identifying specific features of synaptic connectivity that are introduced by precise widening mechanisms during development. In addition, we are introducing a quantitative description of the potential for structural synaptic plasticity for connectivity between different classes of neurons. I propose to study connectivity principles in local circuits of the mammalian brain under the mentorship of Drs. Chklovskii (sponsor) and Svoboda (co-sponsor) at Cold Spring Harbor Laboratory (CSHL). Their laboratories have track record in theoretical and experimental studies of synaptic connectivity. I will work with neuronal pairs and triplets, reconstructed in 3D with Neurolucida in Dr. Chklovskii's laboratory, which will provide a unique opportunity to get insight into the difficult questions of connectivity. This award will give me a chance to focus all my efforts on understanding a very interesting and important biological problem. It will help me enhance my knowledge of experimental and computational neuroscience through hands-on experimental training in CSHL facilities, participation in relevant courses, meetings and conferences, and interaction with leading neuroscience laboratories in the field such as the Chklovskii, Svoboda and Huang laboratories. By the time of the completion of the award I should have the skills and knowledge of experimental techniques necessary to conduct independent research.

描述（由申请人提供）：了解哺乳动物大脑局部回路中的突触连接原理是神经科学中最古老和最重要的问题之一。如果没有对连接原理的清晰了解，就几乎不可能理解大脑的功能或神经回路的变化，而神经回路的变化是神经系统疾病的基础。神经元乔木的形态学保存了关于大脑中突触连接原理的有价值的信息。神经元形态的定量分析可以揭示一些重要的问题：在发育过程中是否存在精确的布线机制，导致成年大脑中特定的连接模式？不同类别神经元之间的连接的结构可塑性潜力是什么？不同种类的神经元寻找突触后伙伴的策略是什么？我们正在制定一种前后一致的方法，这将使我们能够以量化的方式处理这些问题。我们正在建立一种新方法来检测三维（3D）重建的神经元乔木对之间的显着空间相关性。这种方法有可能识别突触连接的具体功能，在开发过程中引入精确的扩大机制。此外，我们正在引入一个定量描述的潜力，结构突触可塑性之间的连接不同类别的神经元。我建议在冷泉港实验室（CSHL）的Chklovskii博士（赞助人）和Svoboda博士（共同赞助人）的指导下研究哺乳动物大脑局部回路的连接原理。他们的实验室在突触连接的理论和实验研究方面有着良好的记录。我将在Chklovskii博士的实验室中使用Neurolucida进行3D重建的神经元对和三联体，这将提供一个独特的机会来深入了解连接的难题。这个奖项将给我一个机会，让我把所有的努力都集中在理解一个非常有趣和重要的生物学问题上。它将帮助我提高我的实验和计算神经科学的知识，通过在CSHL设施动手实验培训，参加相关课程，会议和会议，并与该领域领先的神经科学实验室，如Chklovskii，Svoboda和Huang实验室的互动。到获奖结束时，我应该有必要进行独立研究的实验技术的技能和知识。