Abstract
Extinction is a process that involves new learning that inhibits the expression of previously acquired memories. Although temporarily effective, extinction does not erase an original fear association. Since the extinction trace tends to fade over time, the original memory can resurge. On the other hand, strengthening effects have been described in several reconsolidation studies using different behavioral and pharmacological manipulations. In order to know whether an extinction memory can be strengthened by reactivation-based interventions in the contextual fear conditioning task, we began by replicating the classic phenomenon of spontaneous recovery to show that brief reexposure sessions can prevent the decay of the extinction trace over time in a long-lasting way. This fear attenuation was shown to depend both on L-type calcium channels and protein synthesis, which suggests a reconsolidation process behind the reactivation-induced strengthening effect. The extinction trace was also susceptible to enhancement by a post-reactivation infusion of a memory-enhancing drug (NaB), which was also able to prevent rapid fear reacquisition (savings). These findings point to new reactivation-based approaches able to strengthen an extinction memory to promote its persistence. The constructive interactions between extinction and reconsolidation may represent a promising novel approach in the realm of fear-related disorder treatments.
Highlights
Memory retrieval is a dynamic phenomenon that can, given the right conditions, trigger two distinct processes, reconsolidation or extinction
We demonstrate that a contextual fear extinction memory can be enhanced by brief reactivation sessions
We found that when extinction memory was periodically reactivated, its time-dependent decay was prevented and no spontaneous recovery of fear was verified for at least 28 days (Experiment 2), an effect shown to be mediated by L-type voltage-gated calcium channels (L-VGCC) (Experiment 3)
Summary
Memory retrieval is a dynamic phenomenon that can, given the right conditions, trigger two distinct processes, reconsolidation or extinction. Trace dominance occurs when previously consolidated fear and extinction traces coexist, affecting their retrieval. In such conditions, re-exposure to the CS, which can potentially activate both fear and extinction traces, will result in the expression of the dominant memory and in the inhibition of the other one[2]. There are studies showing that in some tasks reconsolidation only happens when memory is not yet at an asymptotic level[41,42,43], further highlighting its role in the strengthening of the memory trace It is unknown whether a consolidated extinction trace can be modified by reconsolidation
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