Relevance. The studies of the epigenetic mechanisms of long-term memory formation (LTM) has attracted the attention of many world leading laboratories since gained knowledge can be applied to correct cognitive impairments. miRNA dependent suppression of gene expression is the most complicated step in the epigenetic regulation, associated with a huge number of miRNAs (tens of thousands) and the diversity of their targets, thus the knowledge of miRNAs functions during LTM is still very fragmented. Aim. The aim of this study was to investigate the involvement of miRNAs in the formation of long-term memory using the model of the food aversion conditioned reflex development in the mollusk Helix. Prevention of the formation of mature miRNAs via Poly-L-lysine hydrobromide (PLL) treatment - inhibitor of Dicer activity was used as the main approach. Materials and methods. PLL was injected into animals during training, or 1, 3 or 5 hours after training. Success of the formation of conditioned reflexes was tested 72 hours after training. Results. There was a significant deterioration in LTM in animals with injected PLL 1 and 3 hours after training procedure compared with trained animals that were not injected with PLL. The treatment with PLL during training, or 5 hours after training, had no effect on LTM. Conclusion. Treatment with PLL, inhibitor of miRNA biogenesis disrupts formation of the food aversion reflex in Helix. Thus, miNRAs are involved in the LTM formation on Helix. Impaired expression of miRNAs is critical for the long-term memory formation if occurs in the intervals of 1 to 3 hours after training. We can recommend PLL for the investigations in the area of the epigenetic mechanisms of long-term memory.
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