Contextual and temporal regulation of fear memory consolidation in the basolateral amygdala complex

It is widely accepted that fear memories are consolidated through protein synthesis-dependent changes in the basolateral amygdala complex (BLA). However, recent studies show that protein synthesis is not required to consolidate the memory of a new dangerous experience when it is similar to a prior experience. Here, we examined whether the protein synthesis requirement for consolidation of the new experience varies with its spatial and temporal distance from the prior experience. In each experiment, rats were conditioned to fear a stimulus (S1, e.g., light) across its pairings with shock in stage 1; and a second stimulus (S2, e.g., tone) that preceded additional S1-shock pairings (S2-S1-shock) in stage 2. The latter stage was followed by a BLA infusion of a protein synthesis inhibitor, cycloheximide or vehicle. Finally, rats were tested for fear to S2. Critically, protein synthesis in the BLA was not required to consolidate fear to S2 when the two training stages occurred 48 hours apart and in the same context; was required when the two training stages were separated by a 14-day delay or occurred in different contexts; but was again not required when rats were re-exposed to S1 or shock after the delay or in the different context. Thus, protein synthesis in the BLA is not always required to consolidate a new fear memory. Instead, this requirement is determined by the degree of similarity between present and past experiences, the time and place in which those experiences occur, as well as reminders of the past experience. Significance Statement Protein synthesis in the basolateral amygdala complex (BLA) is not required to consolidate the memory of a new dangerous experience when it is similar to a prior experience. This study is significant in showing that: 1) when the new, similar experience occurs after a delay or in a different context, the protein synthesis requirement for its consolidation is reinstated; and 2) the effects of the delay and context shift are reversed by reminding animals of their prior experience. Thus, the neural mechanisms underlying memory consolidation are dynamically regulated by similarity/dissimilarity between present and past experiences, the time and place in which those experiences occur, as well as reminders of the past experience.