Analysis of Activity Propagation in Neural Networks Cultured on Planar Electrode Arrays

培养神经元是研究与生物信息处理相关的脑电活动的有效模型。我们开发了一种利用半导体技术制造的阵列微电极，监测神经元对细胞外电刺激反应的系统。与电压敏感染料记录或玻璃微电极等其他方法相比，该方法侵入性较小，具有多位点记录和电刺激可以持续多天的优点。在这项工作中，我们试图使用该系统来研究神经元如何构成网络结构，以及信息或动作电位的传播模式如何随刺激而变化。将大鼠皮质切片固定在含有64个电极阵列的基质上并进行培养。通过阵列观察切片的活性。结果表明，应用kainic酸可诱导癫痫样活性。特别是深层细胞对活动的贡献增强。此外，从胎鼠新皮层分离的神经元在64个嵌入电极阵列上培养。通过细胞外电极阵列监测神经元对电刺激的反应。从刺激点开始的小活动空间传播后，观察到大的、部分同步的动作电位。为了寻找连接的电极，研究了附近两个电极之间尖峰发生时间模式的相关性。结果表明，多组神经元存在局部连接，且无连接模式，但根据潜伏期的差异，可以直观地看到电位的方向。

Cultured neuron is a useful model for the studies of electrical activites related to biological information processing. We have developed system which monitored the response of neuron to electric stimulus extracellularly through arrayd micro electrodes fabricated using semiconductor technology. This method is less invasive and has the advantage that advantage that multisite recording and electrical stimulation is possible for many days compared with other possibilities, i.e., voltagesensitive dye recording or glass microelectrodes. In this work, using this system we attempted to examine how network structure is constituted by the neurons and how the propagating pattern of information or action potential change by the stimulus.Rat cortial slices were fixed onto substrates containing an array of 64 electrodes and cultured. Activity in the slice was observed through the array. The results suggest that application of kainic acid induces epileptiform activity. Particularly contribution of the cells in deep layrs to activity is enhances.Moreover, neurons dissociated from fetal rat neocotex were cultured on array of 64 embedded electrodes. Response of neuron to electric stimulus were monitored extracellularly through electrode arrays. After the initial propagation of small activity spatially spreading from stimulus point, large and partially synchronized action potentials were observed. To search the connected electrode, the correlation of the occurrence time pattern of spikes at between nearby two electrodes were examined. Results indicated that several group of neurons were locally connected and not pattern of connection, but also the direction of potential could be visualized based on the difference of latency.