Microglia can modulate synapses through processes such as partial phagocytosis of synaptic segments or engulfing entire pre- or postsynaptic elements (76, 77). After observing that ethanol can promote microglial phagocytosis of zymosan and synaptoneurosomes in high-PRS lines, we began to investigate the potential effects of high-PRS microglial cells on synaptic transmission in the context of alcohol consumption. To explore this further, we established a coculture system incorporating human Ngn2-iNs and microglia. Our findings indicated that ethanol enhances excitatory synaptic transmission, which aligns with previous research demonstrating increased glutamatergic activity following chronic alcohol exposure (78). While we did not observe significant changes in synaptic densities in neurons cocultured with microglia compared to neurons without microglia, we did notice that high-PRS microglial cells may contribute to a reduction in excitatory synaptic densities and transmission in neurons following intermittent ethanol exposure. This suggests that high-PRS microglial cells may play a crucial role in shaping synaptic connectivity through a process known as microglia-dependent synapse elimination, specifically in high-PRS individuals, potentially rendering them at higher risk for developing/maintaining AUD. A mouse study (28) has shown
