Searching for Connectivity Principles in the Brain

寻找大脑中的连接原理

• 批准号: 7259504
• 负责人: ARMEN STEPANYANTS
• 金额: $ 12.31万
• 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/7259504
• 关键词: Adult; Award; Axon; Biological; Biological Assay; Brain; Chromosome Pairing; Class; Complex; Detection; Development; Dimensions; Evaluation; Funding; Hand; Interneurons; Knowledge; Laboratories; Lead; Light; Measures; Mentorship; Methodology; Methods; Morphology; Neocortex; Neurons; Neuropil; Neurosciences; Numbers; Pattern; Positioning Attribute; Research; Specificity; Staging; Synapses; Synaptic plasticity; Techniques; Testing; Time; Training; Triplet Multiple Birth; Work; axon guidance; base; computational neuroscience; design; hippocampal pyramidal neuron; insight; interest; laboratory facility; nervous system disorder; neural circuit; postsynaptic; research study; skills; symposium

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(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。如果不清楚连接原理，就几乎不可能理解大脑是如何运作的，也不可能理解神经回路的变化，而神经回路的变化是神经疾病的基础。神经丛的形态包含了关于大脑中突触连接原理的有价值的信息。对神经元形态的定量分析可以阐明一些重要的问题：在发育过程中，是否存在导致成人大脑特定连接模式的精确连接机制？不同类别神经元之间连接的结构可塑性潜势是什么？不同类型的神经元用什么策略来寻找它们的突触后伙伴？我们正在制定一种一致的方法，这将使我们能够以定量的方式处理这些问题。我们正在建立一种新的方法来检测在三维(3D)中重建的神经元树枝对之间的显著空间相关性。这种方法有可能识别突触连接的特定特征，这些特征是在发育过程中由精确的扩大机制引入的。此外，我们还介绍了结构突触可塑性对不同类别神经元之间连接的潜力的定量描述。我建议在Chklovskii博士(发起人)和Svoboda博士(共同发起人)的指导下，在冷泉港实验室(CSHL)研究哺乳动物大脑局部回路中的连接原理。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博士的实验室里与NeuroLucida一起进行神经元对和三胞胎的3D重建，这将提供一个独特的机会，让人们深入了解连接的困难问题。这个奖项将给我一个机会，让我把所有的努力集中在理解一个非常有趣和重要的生物学问题上。它将帮助我通过在CSHL设施中进行动手实验培训，参加相关课程、会议和会议，以及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，来增强我对实验和计算神经科学的知识。在完成该奖项时，我应该具备进行独立研究所需的实验技术的技能和知识。