Memory reconsolidation and amnesia induction: Separate processes dependent on specific protein and RNA synthesis

The reconsolidation hypothesis posits that memory retrieval initiates a phase of memory destabilization, followed by restabilization through protein synthesis-dependent processes. The disruption of reconsolidation by amnestic agents can lead to memory loss. Yet, this hypothesis leaves unanswered questions regarding the mechanisms driving amnesia induction and reversal of molecular and structural changes underlying memory retention. Our previous work proposed that amnesia induction is an active process reliant on both translation and transcription. To test this hypothesis, we explored the role of N-methyl-D-aspartate (NMDA) glutamate receptors, as well as protein and RNA synthesis in amnesia induction mechanisms in grape snails trained with conditional food aversion, during the initial hours following memory reconsolidation disruption. Our results reveal that protein synthesis inhibitor administration before the conditioned reminder stimulus caused amnesia 3 hr after the reminder, whereas NMDA glutamate receptor antagonists resulted in amnesia less than 20 min following the first conditioned reminder stimulus. Concurrent administration of an NMDA receptor antagonist and a protein synthesis inhibitor before the reminder resulted in a rapid (less than 20 min) and complete prevention of amnesia, underscoring the pivotal role of protein synthesis in NMDA-dependent amnesia induction. Conversely, RNA synthesis inhibitors did not affect memory reconsolidation but inhibited amnesia triggered by an NMDA receptor antagonist. Moreover, our study demonstrates a significant difference in the dependency of memory reconsolidation and amnesia induction "time windows" on protein synthesis. These findings lend support to our hypothesis that memory reconsolidation and amnesia represent distinct processes, each characterized by unique developmental dynamics and molecular underpinnings. (PsycInfo Database Record (c) 2024 APA, all rights reserved).