Learning against the Background of DNA Methyltransferase Inhibition Leads to the Formation of Memory That Is Resistant to Reactivation and Impairment.

The involvement of DNA methylation in the mechanisms of formation of conditioned food aversion memory was studied on Helix lucorum snails. The dynamics of aversion formation in snails injected with DNA methyltransferase inhibitor RG108 did not differ from that in control snails. The memory was retained for more than one month after training following RG108 injection and the duration of memory persistence did not differ from that in control animals. However, the characteristics of memory in control and experimental snails differed significantly. In control snails, injections of glutamate NMDA-receptor antagonist or protein synthesis inhibitor before memory retrieval caused disorders in the memory reconsolidation and development of amnesia 2 days after training. By contrast, injections of these substances before retrieval to snails trained against the background of RG108 treatment caused no memory disorders. We hypothesized that inhibition of DNA methylation processes led to the formation of strong memory, not reactivated after retrieval and not transformed into a labile state sensitive to amnesic agents.