Astrocytic control in in vitro and simulated neuron-astrocyte networks

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.