Effect of acute elevated magnesium on bursting activity and information-processing dynamics in cortical cultures

ABSTRACT Magnesium (Mg 2+ ) plays a significant role in hippocampal memory and learning and is implicated in a variety of neurological disorders, such as migraine. Despite this crucial role Mg 2+ has on brain health, its effect on the dynamics of networks of neurons is still not fully understood. This study investigates the impact of several doses of elevated extracellular Mg 2+ on cortical organotypic cultures . Cultures were recorded on a 512-microelectrode array and analyzed using the burstiness index (BI), the rate of network-wide bursts relative to other neuronal activity. We also use a suite of information theoretic measures to further establish the role Mg 2+ plays in the brain. Elevated Mg 2+ is found to have a dose-dependent increase on BI caused by a loss of network activity not contained within a burst or high firing rate activity. Information dynamics further show that the network experiences a loss of entropy and an increase in time-reversibility, connectivity, and transfer of redundant information. These factors indicate that Mg 2+ causes a loss of complex activity and an increase in highly integrated, constant dynamics. This lays the groundwork for a deeper examination of the role Mg 2+ plays in learning, memory and treating neurological disorders. AUTHOR SUMMARY Magnesium is crucial for neurological health. In pyramidal neurons, magnesium blocks NMDA receptors, thereby reducing synchronous neural activity in the brain. This has led to the canonical view of magnesium as a “burst quieter”. Here, we take a closer look at magnesium’s role in cortical slice cultures by examining network burstiness with normal and chronically elevated levels of magnesium. We show that magnesium can effectively increase burstiness, not reduce it. Magnesium is further shown to cause significant changes in how neurons process information. These findings may have impact how magnesium is used as a treatment for neurological disorders.