This work suggests that memory consolidation is a dynamic process that is not unique to the encoding of new memory. In fact, memory retrieval appears to “deconsolidate” established memory traces returning them to a labile and destabilized state that requires protein synthesis-dependent reconsolidation for long-term retention. The mechanisms of deconsolidation are EX527 not known, and it is unclear whether memory reactivation actually reverses the outcome of consolidation or renders the consolidated trace labile in some other way. In either case, interfering with
reconsolidation after retrieval leads to memory loss: the deconsolidated memory fails to stabilize and decays much as short-term memory decays in the absence of consolidation to long-term memory (Figure 3). Although reconsolidation has been described in many memory systems, it is bounded (Nader, 2006). For example, the sensitivity of reactivated memories to protein synthesis inhibitors is related to many factors including the age
and strength of the memory (Milekic and selleck kinase inhibitor Alberini, 2002 and Wang et al., 2009). In addition, not all forms of memory appear to undergo protein synthesis-dependent reconsolidation (Nader and Hardt, 2009). Nonetheless, the sensitivity of long-term fear memories to retrieval-based manipulations provides a much more tractable time window for therapeutic intervention insofar patients with anxiety disorders often seek treatment long after trauma. As a consequence,
several groups have attempted to disrupt consolidated fear memories by interfering nearly with reconsolidation processes after reactivation. Because there is strong interest in developing effective interventions for patients with anxiety disorders, the focus has been on developing interventions that can be safely administered to humans. For example, in rats systemic administration of the beta-adrenergic receptor antagonist, propranolol, disrupts the reconsolidation of fear memories under some conditions (Debiec and Ledoux, 2004 and Muravieva and Alberini, 2010). A pair of studies in humans similarly suggests that propranolol administration can influence the reconsolidation of fear memory. In one report (Kindt et al., 2009), healthy subjects underwent a fear-potentiated startle conditioning procedure followed by oral propranolol administration and memory reactivation the day after conditioning. Interestingly, propranolol disrupted the retention of one index of fear memory (i.e., the conditioned acoustic startle response), but spared declarative memory of the CS-US relationship (i.e., shock expectancy). This effect was not due to propranolol administration alone, insofar as administering propranolol without reactivating the memory did not dampen startle.