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

培养的神经元是研究生物信息处理过程中电活动的一种有用模型。我们研制了一种通过半导体工艺制作的微电极阵列在细胞外监测神经元对电刺激的反应的系统。该方法是侵入性较小的，并且具有以下优点：与其他可能性相比，多部位记录和电刺激可以持续许多天，即，压敏染料记录或玻璃微电极。在本工作中，我们尝试使用该系统来研究神经元是如何构成网络结构的，以及信息或动作电位的传播模式是如何因刺激而改变的。将大鼠皮层切片固定在含有64个电极阵列的基底上并进行培养。通过阵列观察切片中的活性。结果表明，红藻氨酸的应用诱导癫痫样活动。特别是深层细胞对神经活动的贡献增强。此外，从胎鼠皮层分离神经元，在64个埋置电极阵列上进行培养。通过电极阵列在细胞外监测神经元对电刺激的反应。小活动从刺激点空间传播的初始传播后，观察到大的和部分同步的动作电位。为了寻找连接的电极，检查相邻两个电极之间的尖峰出现时间模式的相关性。结果表明，几组神经元之间存在局部连接，但不存在连接模式，而且可以根据潜伏期的差异直观地显示电位的方向。

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.