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（由申请人提供）：下调是海马和帕拉希普门户投影的十字路口，是该地区的主要输出结构。下调是CA3之间的中间复杂性区域，一个具有单层相互连接的锥体神经元的区域，以及6层的Parahippocampal和NeoCortices，该区域与多个主要细胞通过层内和层间环流连接。 CA3的生理研究和建模为基本癫痫发生提供了许多见解。地下的更大的复杂性和位置使其成为研究其他癫痫发作和扩散机制的逻辑下一个结构。我们建议通过将解剖学和生理方法与计算机建模相结合，以评估亚致中的连通性和活动。我们将专注于网络动力学，使用现有结果来定义电池模型的电压敏感和突触通道。这项研究将通过以下特定目的进行：目标1：测量亚丘脑的金字塔和神经元的子阈值和近纹牙地特性，并将其与射击模式和树突状形态相关联。 AIM 2：开发合并和混合的神经网络软件工具和拟合算法以匹配模型与生理学。 AIM 3：定义下锥体细胞的输入/输出关系以兴奋性和抑制性连接。 AIM 4：通过多电极记录和扩展与计算机网络模型的匹配模式探索活动的传播。我们的研究将使我们能够开始定义和分类活动回路中的活动启动，过滤，可置和增强的模式。这将为使用亚致切片和亚致计算机模型作为癫痫模型的阶段。