The mechanisms of memory traces storage and interaction in snails: Role of DNA methylation and protein synthesis

Understanding the molecular mechanisms underlying the storage and interaction of different memory traces remains an important, yet underexplored, topic in neurobiology. We addressed this using grape snails trained to reject two food-conditioned stimuli (CS). Our results indicate that memory storage mechanisms for distinct CS are independent, as selective impairment of memory reconsolidation with an NMDA receptor antagonist affected only one CS. When both CS reconsolidations were simultaneously disrupted, the snails developed amnesia, which manifested as anterograde amnesia on late amnesia stage, where repeated training failed to induce long-term memory formation. Intriguingly, shortened retraining in the presence of a DNA methyltransferase (DNMT) inhibitor facilitated memory recovery for one CS while preserving amnesia for the other, suggesting that latent memory traces are maintained via DNA methylation. Moreover, training to new food type aversion under a DNMT inhibitor induced spontaneous memory recovery for an old CS memory, which was tested the next day after training. This recovery did not occur during new training in the absence of the DNMT inhibitor. It was also found that a protein synthesis inhibitor administered before new training suppressed the restoration of old memory, whereas an inhibitor administered after new training, but not before it, prevented the formation of new memory. These findings demonstrate that independent molecular and epigenetic mechanisms preserve memory traces within the same neuronal ensemble and that new information can reactivate latent memories through specific protein synthesis and DNA methylation processes, offering fresh insights into memory storage and reconsolidation.