PDF(Pubmed)
Abstract：
Brain activity implies the orchestrated functioning of interconnected brain regions. Typical in vitro models aim to mimic the brain using single human pluripotent stem cell-derived neuronal networks. However, the field is constantly evolving to model brain functions more accurately through the use of new paradigms, e.g., brain-on-a-chip models with compartmentalized structures and integrated sensors. These methods create novel data requiring more complex analysis approaches. The previously introduced circular tripartite network concept models the connectivity between spatially diverse neuronal structures. The model consists of a microfluidic device allowing axonal connectivity between separated neuronal networks with an embedded microelectrode array to record both local and global electrophysiological activity patterns in the closed circuitry. The existing tools are suboptimal for the analysis of the data produced with this model. Here, we introduce advanced tools for synchronization and functional connectivity assessment. We used our custom-designed analysis to assess the interrelations between the kainic acid (KA)-exposed proximal compartment and its nonexposed distal neighbors before and after KA. Novel multilevel circuitry bursting patterns were detected and analyzed in parallel with the inter- and intracompartmental functional connectivity. The effect of KA on the proximal compartment was captured, and the spread of this effect to the nonexposed distal compartments was revealed. KA induced divergent changes in bursting behaviors, which may be explained by distinct baseline activity and varied intra- and intercompartmental connectivity strengths. The circular tripartite network concept combined with our developed analysis advances importantly both face and construct validity in modeling human epilepsy in vitro.
摘要：
大脑活动意味着相互关联的大脑区域的协调功能。典型的体外模型旨在使用单个人多能干细胞衍生的神经元网络来模拟大脑。然而,该领域正在不断发展，通过使用新的范式来更准确地模拟大脑功能，例如，具有分隔结构和集成传感器的芯片上大脑模型。这些方法创建了需要更复杂分析方法的新数据。先前引入的圆形三方网络概念对空间多样的神经元结构之间的连通性进行了建模。该模型由微流体装置组成，该装置允许具有嵌入式微电极阵列的分离的神经元网络之间的轴突连接，以记录闭合电路中的局部和全局电生理活动模式。现有工具对于使用该模型生成的数据的分析是次优的。这里,我们引入了用于同步和功能连接评估的高级工具。我们使用定制设计的分析来评估在KA之前和之后暴露于海藻酸（KA）的近端隔室与其未暴露的远端邻居之间的相互关系。与房间和房内功能连通性并行地检测和分析了新颖的多级电路突发模式。KA对近端隔室的影响被捕获，并揭示了这种效应向未暴露的远端隔室的传播。KA诱导了爆裂行为的发散变化，这可以通过不同的基线活动和不同的室内和室间连接强度来解释。圆形三方网络概念与我们开发的分析相结合，在体外对人类癫痫进行建模时，重要的是正面和构造有效性。
