Astrocytes and neurons respond to each other by releasing transmitters, such as γ-aminobutyric acid (GABA) and glutamate, that modulate the synaptic transmission and electrochemical behavior of both cell types. Astrocytes also maintain neuronal homeostasis by clearing neurotransmitters from the extracellular space. These astrocytic actions are altered in diseases involving malfunction of neurons, e.g., in epilepsy, Alzheimer’s disease, and Parkinson’s disease. Convulsant drugs such as 4-aminopyridine (4-AP) and gabazine are commonly used to study epilepsy in vitro. In this study, we aim to assess the modulatory roles of astrocytes during epileptic-like conditions and in compensating drug-elicited hyperactivity. We plated rat cortical neurons and astrocytes with different ratios on microelectrode arrays, induced seizures with 4-AP and gabazine, and recorded the evoked neuronal activity. Our results indicated that astrocytes effectively counteracted the effect of 4-AP during stimulation. Gabazine, instead, induced neuronal hyperactivity and synchronicity in all cultures. Furthermore, our results showed that the response time to the drugs increased with an increasing number of astrocytes in the co-cultures. To the best of our knowledge, our study is the first that shows the critical modulatory role of astrocytes in 4-AP and gabazine-induced discharges and highlights the importance of considering different proportions of cells in the cultures.

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Astrocytes-a prominent glial cell type in the brain-form networks that tightly interact with the brain's neuronal circuits. Thus, it is essential to study the modes of such interaction if we aim to understand how neural circuits process information. Thereby, calcium elevations, the primary signal in astrocytes, propagate to the adjacent neighboring cells and directly regulate neuronal communication. It is mostly unknown how the astrocyte network topology influences neuronal activity. Here, we used a computational model to simulate planar and 3D neuron-astrocyte networks with varying topologies. We investigated the number of active nodes, the shortest path, and the mean degree. Furthermore, we applied a graph coloring analysis that highlights the network organization between different network structures. With the increase of the maximum distance between two connected astrocytes, the information flow is more centralized to the most connected cells. Our results suggest that activity-dependent plasticity and the topology of brain areas might alter the amount of astrocyte controlled synapses.

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