Effective Connectivity of Hippocampal Neural Network and Its Alteration in Mg2+-Free Epilepsy Model

Understanding the connectivity of the brain neural network and its evolution in epileptiform discharges is meaningful in the epilepsy researches and treatments. In the present study, epileptiform discharges were induced in rat hippocampal slices perfused with Mg2+-free artificial cerebrospinal fluid. The effective connectivity of the hippocampal neural network was studied by comparing the normal and epileptiform discharges recorded by a microelectrode array. The neural network connectivity was constructed by using partial directed coherence and analyzed by graph theory. The transition of the hippocampal network topology from control to epileptiform discharges was demonstrated. Firstly, differences existed in both the averaged in- and out-degree between nodes in the pyramidal cell layer and the granule cell layer, which indicated an information flow from the pyramidal cell layer to the granule cell layer during epileptiform discharges, whereas no consistent information flow was observed in control. Secondly, the neural network showed different small-worldness in the early, middle and late stages of the epileptiform discharges, whereas the control network did not show the small-world property. Thirdly, the network connectivity began to change earlier than the appearance of epileptiform discharges and lasted several seconds after the epileptiform discharges disappeared. These results revealed the important network bases underlying the transition from normal to epileptiform discharges in hippocampal slices. Additionally, this work indicated that the network analysis might provide a useful tool to evaluate the neural network and help to improve the prediction of seizures.