Towards a Complete Description of the Circuitry Underlying Memory replay.

实现内存重放底层电路的完整描述。

• 批准号: 8935978
• 负责人: IVAN SOLTESZ
• 金额: $ 70.7万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-30 至 2017-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8935978
• 关键词: Area; Behavioral; Brain; Brain region; Cells; Computer Simulation; Data; Detection; Episodic memory; Event; Generations; Health; Hippocampus (Brain); Image; Interneurons; Invertebrates; Measurement; Measures; Medial; Mediating; Memory; Memory Disorders; Methods; Modeling; Neurons; Optical Methods; Optics; Pattern; Process; Property; Pyramidal Cells; Radial; Recurrence; Role; Running; Synapses; System; Technology; Test Result; Testing; Time; Transfection; Work; arm; base; brain cell; cell type; cognitive function; dentate gyrus; entorhinal cortex; in vivo; insight; interest; meetings; memory recall; novel; novel strategies; optical imaging; optogenetics; reconstitution; research study; supercomputer; tool

 DESCRIPTION (provided by applicant): The function of a brain region is an emergent property of many cell types. The criteria needed to understand a network have been established in studies of invertebrate "simple" networks, but there has not yet been an attempt to provide such a full, mechanistic understanding of any network in the vertebrate brain. We believe that the time is now ripe for such an effort. Specifically, we propose to understand how the CA3 network in the hippocampus generates sharp-wave-ripples (SWR). These events are of great interest because of their cognitive function: they represent replay of episodic memory sequences and are required for subsequent memory recall, as demonstrated at the behavioral level. Our efforts to understand the SWR will build on previous work establishing the cell types of the hippocampus. However, to meet the criteria for "understanding", a great deal of additional information about connectivity and intrinsic properties of cells must be obtained. We will use recently developed large-scale electrical and optical recording methods and ontogenetic to obtain this information. In addition, several new methods/tools will be developed. Notably, we propose to optimize a novel synapse localization optical method to obtain high-throughput cell type-specific information about the connective of the CA3 network. We will also construct the first full-scale computational model of the CA3 region of the hippocampus, in which every cell and synaptic connection is explicitly represented. This strictly data-driven, full-scale model will provide a widely applicable tool for synthesizing experimental results and testing our ability to understand the principles that underlie SWR generation.

 描述（由适用提供）：大脑区域的功能是许多细胞类型的紧急特性。在无脊椎动物“简单”网络的研究中已经建立了网络所需的标准，但是尚未尝试提供对脊椎动物大脑中任何网络的完整机械理解。我们认为，现在的努力已经成熟了。具体而言，我们建议了解海马中的CA3网络如何产生锋利的波 - 纹状体（SWR）。由于其认知功能，这些事件引起了极大的兴趣：它们代表了情节记忆序列的重播，这是在行为层面上所证明的后续记忆召回所必需的。我们为了解SWR的努力将基于建立海马细胞类型的先前工作。但是，要符合“理解”的标准，必须获得有关细胞连通性和内在特性的大量其他信息。我们将使用最近开发的大规模电和光学记录方法和个体遗传学来获取此信息。此外，还将开发几种新的方法/工具。值得注意的是，我们建议优化一种新型的突触定位光学方法，以获取有关CA3网络连接的高通量细胞类型特定信息。我们还将构建海马CA3区域的第一个全尺度计算模型，其中每个单元和突触连接都被明确表示。这种严格的数据驱动，全尺度模型将 提供一个广泛适用的工具，用于综合实验结果并测试我们了解SWR生成的原理的能力。