Exploring the form- And time-dependent effect of low-frequency electromagnetic fields on maintenance of hippocampal long-term potentiation

Low-frequency electromagnetic field (LF-EMF) stimulation is an emerging neuromodulation tool that is attracting more attention because of its non-invasive and well-controlled characteristics. However, the effect of different LF-EMF features including the forms and the time of addition on neuronal activity has not been completely understood. In this study, we used multi-electrode array (MEA) systems to develop a flexible in vitro magnetic stimulation device with plug-and-play features that allows for real-time delivery of LF-EMFs to biological tissues. Crucially, the method enables different forms of LF-EMF to be added at any time to a long-term potentiation (LTP) experiment without interrupting the process of LTP induction. We demonstrated that the slope of field excitatory postsynaptic potentials (fEPSPs) decreased significantly under post or priming uninterrupted sine LF-EMFs. The fEPSPs slope would continue to decline significantly when LF-EMFs were added two times with a 20-min interval. Paired-pulse ratio (PPR) was analyzed and the results reflected that LF-EMFs induced LTP was expressed postsynaptically. The results of pharmacological experiments indicated that AMPA receptor activity was involved in the process of LTP loss caused by post-LF-EMFs. Moreover, the effect of priming sine or Quadripulse stimulation (QPS)-patterned LF-EMFs depended on the time interval between the end of LF-EMF and the beginning of baseline recording. Interestingly, the effect of sine LF-EMFs on LTP would not disappear within 120 min, while the impact of QPS-patterned LF-EMFs on LTP might disappear after 90 min. These results indicated that LF-EMF might have a form- and time-dependent effect on LTP.