Anisomycin and the reconsolidation hypothesis.

For over 30 years researchers have suspected that the very act of retrieving a memory places it in a labile state and leaves it vulnerable to subsequent challenges that affect the brain. Misanin et al. (1968) provided the initial empirical basis for this claim when they reported that electroconvulsive shock (ECS) presented immediately following a brief presentation of a fear-conditioned CS produced retrograde amnesia for the fear memory, whereas ECS alone had no effect on the fear memory. Thus, a memory in an active state appeared to be more vulnerable to the effects of an amnesia-producing event than when it is in an inactive state (Lewis 1979). This basic empirical claim was followed by controversy over both its repeatability and generality (e.g., Dawson and McGaugh 1969) and its proper theoretical interpretation: Was the resulting amnesia due to the destruction of the memory trace or did the amnestic agent just render the memory temporarily inaccessible (see Miller and Springer 1973)? Perhaps for these reasons research interest in these phenomena lay dormant until fairly recently. Interest in the fate of reactivated memories dramatically increased with the recent work of Nader and his colleagues (Nader et al. 2000; Debiec et al. 2002; Nader 2003) and Przybyslawski and Sara (1997). In their seminal paper, Nader et al. (2000) reactivated an auditory-cue fear memory and then injected the antibiotic, anisomycin, a protein synthesis inhibitor, or vehicle into the basolateral region of the amygdala (BLA). Subsequent retesting with the CS revealed that anisomycin produced amnesia for the reactivated fear memory. Anisomycin given without reactivating the memory had no effect.