Reverse Engineering Cortical Circuitry

逆向工程皮质电路

• 批准号: 6915741
• 负责人: William W Lytton
• 金额: $ 25.85万
• 依托单位: SUNY DOWNSTATE MEDICAL CENTER
• 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 2008-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6915741
• 关键词: albino rat; bioengineering /biomedical engineering; cell morphology; computational neuroscience; computer program /software; computer simulation; computer system design /evaluation; dendrites; electrodes; electrophysiology; epilepsy; hippocampus; interneurons; model design /development; neuroanatomy; neurophysiology; pyramidal cells; sectioning; single cell analysis; tissue /cell preparation

DESCRIPTION (provided by applicant): The subiculum is a crossroads of hippocampal and parahippocampal projections, and the major output structure of the region. The subiculum is a region of intermediate complexity between CA3, a region with a single layer of interconnected pyramidal neurons, and the 6-layered parahippocampal and neocortices, regions with multiple principal cells connected via intralaminar and interlaminar circuits. Physiological investigation and modeling of CA3 has provided many insights into basic epileptogenesis. The greater complexity and location of subiculum makes it a logical next structure for study of additional mechanisms of seizure origin and spread. We propose to evaluate connectivity and activity spread in subiculum by combining anatomical and physiological methods with computer modeling. We will focus on network dynamics, using existing results to define voltage-sensitive and synaptic channels for the cell models. The research will proceed via the following specific aims: AIM 1: Measure subthreshold and suprathreshold properties of pyramidal and interneurons of subiculum and relate these to firing patterns and dendritic morphology. AIM 2: Develop combined and hybrid neural network software tools and fitting algorithms to match models to physiology. AIM 3: Define input/output relations for subicular pyramidal cells to excitatory and inhibitory connections. AIM 4: Explore spread of activity with multi-electrode recordings and match patterns of spread to the computer network model. Our research will allow us to begin to define and classify patterns of activity initiation, filtering, sustention and boosting in cortical circuits. This will set the stage for use of the subiculum slice and subiculum computer model as an epilepsy model.

描述(申请人提供)：下丘是海马区和副海马区投射的交叉点，也是该区域的主要输出结构。下丘是介于CA3区和6层海马旁皮质和新皮质之间的中等复杂区域，CA3区由单层相互连接的锥体神经元组成，6层海马旁皮质和新皮质区由多个主细胞通过板内和板间回路连接。CA3的生理学研究和建模为癫痫的基本发病机制提供了许多新的见解。下丘的更大的复杂性和位置使它成为研究癫痫起源和传播的其他机制的下一个合理的结构。我们建议通过将解剖学和生理学方法与计算机建模相结合来评估下丘脑的连通性和活动分布。我们将专注于网络动力学，使用现有的结果来定义细胞模型的电压敏感和突触通道。本研究将通过以下具体目标进行：目标1：测量下丘脑锥体和中间神经元的阈值下和阈值上特性，并将其与放电模式和树突形态相关联。目的2：开发组合和混合神经网络软件工具和拟合算法，使模型与生理匹配。目的3：确定下丘脑锥体细胞兴奋性和抑制性联系的输入/输出关系。目的4：用多电极记录探索活动的传播，并将传播模式与计算机网络模型相匹配。我们的研究将使我们能够开始定义和分类皮层环路中活动的启动、过滤、维持和增强模式。这将为使用下丘脑片和下丘脑片计算机模型作为癫痫模型奠定基础。