Contribution of histone acetylation to the serotonin-mediated long-term synaptic plasticity in terrestrial snails

Serotonin plays a decisive role in long-term synaptic plasticity and long-term memory in mollusks. Previously, we demonstrated that histone acetylation is a critical regulatory mechanism of long-term memory in terrestrial snail. At the behavioral level, many studies were done in Helix to elucidate the role of histone acetylation and serotonin. However, the impact of histone acetylation on long-term potentiation of synaptic efficiency in electrophysiological studies in Helix has been studied only in one paper. Here we investigated effects of serotonin, histone deacetylases inhibitors sodium butyrate and trichostatin A, and a serotonergic receptor inhibitor methiothepin on long-term potentiation of synaptic responses in vitro. We demonstrated that long-term potentiation was suppressed by methiothepin but rescued by co-application of histone deacetylase inhibitors sodium butyrate or trichostatin A. Increased histone acetylation compensated the loss of serotonergic activation. We showed that single serotonin application in combination with histone deacetylase blockade could mimic the effect of repeated serotonin applications and be enough for sustained long-lasting synaptic changes. The data obtained demonstrated that histone deacetylases blockade ameliorated deficits in synaptic plasticity induced by different paradigms (methiothepin treatment, the weak training protocol with single application of serotonin), suggesting that histone acetylation contributes to the serotonin-mediated synaptic plasticity.