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

• Published in: Neurobiology of learning and memory Vol. 200; p. 107733
• Main Authors: Urrego-Morales, Oscar, Gil-Lievana, Elvi, Ramirez-Mejia, Gerardo, Francisco Rodríguez-Durán, Luis, Lilia Escobar, Martha, Delint-Ramirez, Ilse, Bermúdez-Rattoni, Federico
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.04.2023
• Subjects: Acquisition; Acyltransferases - metabolism; Consolidation; Hippocampus - physiology; Maze Learning - physiology; Memory Consolidation - physiology; Palmitoylation; Spatial Learning - physiology; Spatial memory; Spatial Memory - physiology; OLM; MWM; Consolidation; HFS; Palmitoylation; PATs; LTP; Acquisition; LTD; HIP; Spatial memory
• ISSN: 1074-7427; 1095-9564
• DOI: 10.1016/j.nlm.2023.107733

•Palmitoyl acyltransferase activity in the hippocampus is necessary for the acquisition and consolidation, but not for the retrieval of spatial memory tasks.•Synaptic plasticity, as measured by long-term potentiation in the Schaffer Collateral pathway, requires palmitoyl acyltransferase activity for the LTP induction but not for the LTP maintenance. 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.