Unveiling the impact of low-frequency electrical stimulation on network synchronization and learning behavior in cultured hippocampal neural networks

Understanding the dynamics of neural networks and their response to external stimuli is crucial for unraveling the mechanisms associated with learning processes. In this study, we hypothesized that electrical stimulation (ES) would lead to significant alterations in the activity patterns of hippocampal neuronal networks and investigated the effects of low-frequency ES on hippocampal neuronal populations using the microelectrode arrays (MEAs). Our findings revealed significant alterations in the activity of hippocampal neuronal networks following low-frequency ES trainings. Post-stimulation, the neural activity exhibited an organized burst firing pattern characterized by increased spike and burst firings, increased synchronization, and enhanced learning behaviors. Analysis of peri-stimulus time histograms (PSTHs) further revealed that low-frequency ES (1Hz) significantly enhanced neural plasticity, thereby facilitating the learning process of cultured neurons, whereas high-frequency ES (>10Hz) impeded this process. Moreover, we observed a substantial increase in correlations and connectivity within neuronal networks following ES trainings. These alterations in network properties indicated enhanced synaptic plasticity and emphasized the positive impact of low-frequency ES on hippocampal neural activities, contributing to the brain's capacity for learning and memory. •The hippocampal neural networks were cultured in vitro on microelectrode arrays, to directly measure the electrophysiological changes of the cultured networks induced by the external electrical stimulation.•The peri-stimulus time histograms (PSTHs) analysis was conducted, to study the instant response of neurons to the external electrical stimulations, and it demonstrated that only the low-frequency (1Hz) electrical stimulation could facilitate the learning process of the hippocampal neurons.•The cluster analysis was implemented to classify the neurons into interneuron and pyramidal neuron, and the effects of electrical stimulation impacting on them were analyzed respectively.•The cross-correlation based method was used to assess the correlation and connectivity of the neural networks, and the results showed that the ES trainings had significantly increased the correlation as well as the connectivity of the networks.