Context and time regulate fear memory consolidation and reconsolidation in the basolateral amygdala complex

Abstract

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 isnotrequired 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 consolidating the new experience varies with its spatial and temporal distance from the prior experience. Female and male rats were conditioned to fear a stimulus (S1, e.g., light) paired 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. Subsequent testing with S2 revealed that protein synthesis in the BLA: wasnotrequired to consolidate fear to S2 when the two training stages occurred 48-hours apart in the same context;wasrequired when they were separated by a 14-day delay or occurred in different contexts; but was againnotrequired if S1 was re-presented after the delay or in the different context. Similarly, protein synthesis in the BLA wasnotrequired toreconsolidate fear to S2 when the training stages occurred 48-hours apart, butwasrequired when they occurred 14-days apart. Thus, the protein synthesis requirement for consolidating/reconsolidating fear memories in the BLA is determined by the similarity between present and past experiences, the time and place in which they occur, and reminders of the past experiences.Significance StatementProtein synthesis in the basolateral amygdala complex (BLA) isnotrequired 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 experience occurs after a delay or in a different context, the protein synthesis requirement is reinstated; (2) the effects of the delay and context shift are reversed by reminding animals of their prior experience; and (3) the delay affects reconsolidation of a new experience in the same way that it affects the initial consolidation. Thus, the neural mechanisms underlying memory are regulated by similarity/dissimilarity between present and past experiences, the time/place in which those experiences occur, and reminders of past experience.