DNA Methylation and Histone Acetylation Contribute to the Maintenance of LTP in the Withdrawal Behavior Interneurons in Terrestrial Snails

Accumulated data indicate that epigenetic regulations, including histone modifications and DNA methylation, are important means for adjusting genes’ expression in response to various stimuli. In contrast to the success in studying the role of DNA methylation in laboratory rodents, the role of DNA methylation in terrestrial snail Helix lucorum has been studied only in behavioral experiments. This prompted us to further investigate the role of DNA methylation and the interaction between DNA methylation and histone acetylation in the mechanisms of neuroplasticity in terrestrial snails using in vitro experiments. Dysregulation of DNA methylation by DNMT inhibitor RG108 suppressed significantly the long-term potentiation (LTP) of synaptic inputs in identified neurons. We then tested whether the RG108-induced weakening of potentiation will be rescued under co-application of histone deacetylase inhibitors sodium butyrate or trichostatin A. RG108-induced LTP deficiency was significantly compensated by increased histone acetylation. These data bring important insight to the functional role of DNA methylation as an important regulatory mechanism and a necessary condition for the development and maintenance of long-term synaptic changes in withdrawal interneurons of terrestrial snails. Moreover, these results support the idea of the interaction of DNA methylation and histone acetylation in the epigenetic regulation of synaptic plasticity.