Reverse Engineering Cortical Circuitry

描述（由申请人提供）：下托是海马和海马旁投射的十字路口，是该区域的主要输出结构。下托是介于CA 3和6层海马旁和新皮质之间的中间复杂性区域，CA 3是具有单层相互连接的锥体神经元的区域，6层海马旁和新皮质是具有通过板内和层间回路连接的多个主细胞的区域。CA 3的生理学研究和建模为基本癫痫发生提供了许多见解。更大的复杂性和位置的下托，使其成为一个合乎逻辑的下一个结构的研究癫痫发作的起源和传播的其他机制。我们建议通过结合解剖学和生理学方法与计算机建模来评估下托的连通性和活动传播。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。研究将通过以下具体目标进行：目的1：测量阈下和阈上特性的锥体和中间神经元的下托和这些相关的放电模式和树突形态。目的2：开发组合和混合神经网络软件工具和拟合算法，以匹配模型的生理。目的3：明确下托锥体细胞对兴奋性和抑制性连接的输入/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的模式，活动启动，过滤，维持和促进皮层电路。这将为使用下托切片和下托计算机模型作为癫痫模型奠定基础。

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.