Microglial activation drives neuronal dysregulation in alcohol-induced seizure susceptibility.

Excessive alcohol drinking can induce seizures, but the mechanisms underlying acute alcohol-induced seizures remained to be extensively investigated. To investigate this, we established an acute alcohol-treated model and observed a microglial response in the hippocampal CA1 region of mice, which was associated with the enhancement of seizure susceptibility. Furthermore, we found an increased abundance of GABAergic interneurons and a decrease in the activity of CaMKII in the hippocampal CA1 region. Minocycline-mediated microglial depletion fully inhibited the increase in GABAergic interneurons and GABAergic inhibitory synapse formation, and the decrease in glutamatergic neurons and glutamatergic excitatory synapse formation induced by acute alcohol treatment. In conclusion, our findings indicate that dysregulation of synapse formation via microglial activation contributes to acute alcohol-induced enhancement of seizure susceptibility.