Erasing fear memories with extinction training

Abstract

Decades of behavioral studies have confirmed that extinction does not erase classically conditioned fear memories. For this reason, research efforts have focused on the mechanisms underlying the development of extinction-induced inhibition within fear circuits. However, recent studies in rodents have uncovered mechanisms that stabilize and destabilize fear memories, opening the possibility that extinction might be used to erase fear memories. This symposium focuses on several of these new developments, which involve the timing of extinction training. Extinction-induced erasure of fear occurs in very young rats, but is lost with the development of perineuronal nets in the amygdala that render fear memories impervious to extinction. Moreover, extinction administered during the reconsolidation phase, when fear memory is destabilized, updates the fear association as safe, thereby preventing the return of fear, in both rats and humans. The use of modified extinction protocols to eliminate fear memories complements existing pharmacological strategies for strengthening extinction.

Figure 1.

Schemas showing how different extinction procedures might interact with fear memory. A, Under standard conditions, extinction erases fear in very young rats (<24 d of age). Above this age, extinction leaves the fear memory intact but inhibits its expression. The transition corresponds to the development of PNNs in the amygdala. B, Extinction with pharmacological (pharm.) adjuncts such as d-cycloserine strengthens extinction, but still leaves fear memories intact. C, Administering extinction shortly after a reactivation of the fear memory, during its reconsolidation (reconsol.) window, erases the original fear memory, converting it to a safety memory. Blue shading represents the strength of the fear memory.