Inhibition of hippocampal palmitoyl acyltransferase activity impairs spatial learning and memory consolidation

Protein palmitoylation regulates trafficking, mobilization, localization, interaction, and distribution of proteins through the palmitoyl acyltransferases (PATs) enzymes. Protein palmitoylation controls rapid and dynamic changes of the synaptic architecture that modifies the efficiency and strength of synaptic connections, a fundamental mechanism to generate stable and long-lasting memory traces. Although protein palmitoylation in functional synaptic plasticity has been widely described, its role in learning and memory processes is poorly understood. In this work, we found that PATs inhibition into the hippocampus before and after the training of Morris water maze (MWM) and object location memory (OLM) impaired spatial learning. However, we demonstrated that PATs inhibition during the retrieval does not affect the expression of spatial memory in both MWM and OLM. Accordingly, long-term potentiation induction is impaired by inhibiting PATs into the hippocampus before high-frequency electrical stimulation but not after. These findings suggest that PATs activity is necessary to modify neural plasticity, a mechanism required for memory acquisition and consolidation. Like phosphorylation, active palmitoylation is required to regulate the function of already existing proteins that change synaptic strength in the hippocampus to acquire and later consolidate spatial memories.

Automated summary

Protein palmitoylation, mediated by PATs enzymes, regulates various aspects of protein function, including trafficking, mobilization, localization, interaction, and distribution. This process plays a crucial role in modifying synaptic architecture and altering synaptic connections, thereby influencing memory formation and retrieval. In this study, inhibition of PATs in the hippocampus impaired spatial learning, but did not affect memory expression during retrieval. Additionally, inhibiting PATs before electrical stimulation impaired long-term potentiation induction. These findings suggest that PATs activity is essential for neural plasticity, which is required for memory acquisition and consolidation.