Astrocytic control in in vitro and simulated neuron-astrocyte networks

B. Genocchi, A. Ahtiainen, Michael Taynnan Barros, J. Tanskanen, J. Hyttinen, K. Lenk
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Abstract

Astrocytes are involved in the information propagation in the brain by interacting with neurons. Computational modeling helps to study the underlying mechanisms for this communication deeply. In this work, we aimed to analyze how the number of astrocytes and the resulting astrocytic network structure affects neuronal activity. Therefore, we conducted in vitro experiments with microelectrode arrays and simulations with our previously published computational neuron-astrocyte network model side-by-side. In those, we included neuronal cultures without supplemented astrocytes and three conditions with co-cultures where different amounts of astrocytes were added. We then conducted a cross-correlation analysis between the single-channel spike trains and a graph analysis, which included the mean degree, mean shortest path, and the number of nodes, based on the highly correlated channels. Furthermore, we combined the cross-correlation network analysis of the simulated data and the structure of the astrocyte topology. Our experimental results showed that the spike rate was very variable and higher in cultures without added astrocytes than overall in co-cultures. In the co-cultures, the activity was elevated with an increasing number of astrocytes. Additionally, the spike rate was correlated with the mean degree of the neuronal network. This correlation was smaller with larger numbers of astrocytes in the culture. The simulations showed that the most active neurons were localized in the center of the network, which were, however, not always the most connected ones. The astrocytic activation was mainly driven by the vicinity to highly active neurons rather than from the activation through gap junctions. To conclude, the co-cultures with added astrocytes showed stabilization of neuronal activity. Furthermore, increasing the number of astrocytes led to a higher neuronal activity, indicating a feedback excitation loop between astrocytes and neurons.
星形胶质细胞体外控制和模拟神经元-星形胶质细胞网络
星形胶质细胞通过与神经元的相互作用参与大脑信息的传播。计算建模有助于深入研究这种通信的底层机制。在这项工作中,我们旨在分析星形胶质细胞的数量和由此产生的星形胶质细胞网络结构如何影响神经元活动。因此,我们用微电极阵列进行了体外实验,并用我们之前发表的计算神经元-星形胶质细胞网络模型进行了模拟。在这些实验中,我们包括没有补充星形胶质细胞的神经元培养和三种添加不同数量星形胶质细胞的共培养。然后,我们对单通道尖峰序列进行了互相关分析,并基于高度相关通道进行了图分析,包括平均程度、平均最短路径和节点数量。此外,我们将模拟数据的相互关联网络分析与星形细胞拓扑结构相结合。我们的实验结果表明,峰值率变化很大,在没有添加星形胶质细胞的培养中比在共培养中总体更高。在共培养中,活性随着星形胶质细胞数量的增加而升高。此外,峰值速率与神经元网络的平均程度相关。这种相关性随着培养中星形胶质细胞数量的增加而减小。模拟显示,最活跃的神经元位于网络的中心,然而,这些中心并不总是连接最紧密的神经元。星形细胞的激活主要是由高度活跃的神经元附近驱动的,而不是通过间隙连接激活的。综上所述,添加星形胶质细胞的共培养显示出神经元活性的稳定。此外,星形胶质细胞数量的增加导致神经元活动的增加,表明星形胶质细胞和神经元之间存在反馈兴奋回路。
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