NAT10 Inhibition as a Potential Modulator of Long-Term Memory Consolidation in Drosophila melanogaster

Long-term memory (LTM) consolidation depends on protein synthesis and cytoskeletal remodeling. The acetyltransferase NAT10 may contribute to these processes via acetylation of microtubules and mRNA. Inhibition of NAT10 (iNAT10) with Remodelin has been shown to prevent neurodegeneration in tauopathy models, yet its role in learning and memory remains unexplored. Here, we ask whether iNAT10 facilitates LTM consolidation in Drosophila, using an under-predation training paradigm with the jumping spider Menemerus semilimbatus. We first established a weak-training protocol by exposing w1118 flies to the predator for 1 h and assessing memory retention 24 h later. Unlike the established strong-training protocol (2 h), weak training failed to induce LTM. Preliminary results indicate that post-training administration of Remodelin can facilitate memory consolidation following weak training, as assessed by kymographic analysis of population motor activity. To further characterize the effects of iNAT10 on memory consolidation, we will assess an additional defensive strategy elicited by spider predation: place preference. Specifically, 24 h after training, flies will be tested for their preference between a compartment previously associated with the predator and one inaccessible to it. These findings establish a behavioral framework for investigating the role of NAT10 in LTM consolidation, and whether this mechanism can be harnessed to rescue or enhance memory in pathological models.