Figure 2.

Phases of fear memory and their modulation to reduce fear expression. Blue arrows/text represent normal memory processes; red arrows/text represent interventions to reduce fear expression. (A) Phases of fear memory. Consolidation of a memory after its acquisition (Acq) stabilises the long-term memory (LTM) and thereby increases memory expression. Mechanisms of memory maintenance enable the consolidated memory to persist. Reactivation of a LTM can lead to its destabilisation, necessitating a process of reconsolidation to restabilise the memory again into a persistent long-term form (post-reactivation LTM, PR-LTM). Exposure to fear stimuli in the absence of the aversive outcome results in extinction that suppresses memory expression. (B) Impairment of consolidation to erase fear memories. Interference with the cellular mechanisms that are required to consolidate a newly acquired memory can prevent the formation of LTM; the memory trace instead decays, leading to reduced memory expression. (C) Impairment of memory maintenance to erase fear memories. Interference with the cellular mechanisms of memory maintenance leads to rapid erasure of the memory and hence decay of memory expression. (D) Impairment of reconsolidation to erase fear memories. Interference with the cellular mechanisms of memory reconsolidation prevents a destabilised memory from being successfully restabilised; the destabilised memory instead decays, leading to reduced memory expression. (E) Enhancement of extinction as a compensatory mechanism to reduce fear. An extinguished memory normally recovers easily. However, pharmacological enhancement of extinction results in a persistent reduction in fear memory expression that appears not to recover.