Generalization and recovery of post-retrieval amnesia.

Abstract

Selective amnesia for previously established memories can be induced by administering drugs that impair protein synthesis shortly after memory reactivation. Competing theoretical accounts attribute this selective post-retrieval amnesia to drug-induced engram degradation (reconsolidation blockade) or to incorporation of sensory features of the reactivation experience into the memory representation, hampering later retrieval in a drug-free state (memory integration). Here we present evidence that critically challenges both accounts. In contextual fear conditioning in rats, we find that amnesia induced by administration of midazolam (MDZ) after re-exposure to the training context A generalizes readily to a similar context B. Amnesia is also observed when animals are exposed to the similar context B prior to MDZ administration and later tested for fear to context B, but recovers when instead testing for fear to the original training context A or an equally similar but novel context C. Next to their theoretical implications for the nature of forgetting, our findings raise important questions about the viability of reconsolidation-based interventions for the treatment of emotional disorders.

Covert capture and attenuation of a hippocampus-dependent fear memory

“…Although our results suggest that clinical interventions that rely on indirect retrieval methods (such as imaginal exposure) may be effective for opening a window to modify, edit or erase neural representations of unwanted traumatic fear memories, an important question is whether indirectly reactivated memories are sensitive to amnesic agents during reconsolidation 26 . Given that memories integrate into complex associative structures (including outside the hippocampus), it is unclear if the reactivation of one element of the associative network results in the reactivation of other parts of the associative network in a way that renders them sensitive to reconsolidation manipulations.…”

Effects of repeated anodal transcranial direct current stimulation on auditory fear extinction in C57BL/6J mice

“…Placing mice in the renewal context is expected to reactivate the initial fear memory, since extinction training does not erase this initial CS þ -US association but depends on the formation of a new contextdependent extinction memory [35,84,85]. Indeed, in extinction [86,87], reconsolidation [88] and reactivation-extinction [89] based procedures, recovery of fear has been observed, illustrating that Modulation of auditory fear extinction and generalization with repeated anodal tDCS in experiments with a shock intensity of 1 mA during fear conditioning. The graphs illustrate the freezing responses of sham and tDCS mice during the acclimation period (HAB) or evoked by cue presentation (CS À , CS þ ) in the fear retrieval, extinction training, early extinction recall, late extinction recall and the fear renewal test.…”

A critical assessment of reconsolidation interference as a tool for therapeutic forgetting

“…Although reconsolidation theory has dominated the field, it has not been free from debate. It has been suggested that not all behavioral effects observed after combining a reminder with an amnestic manipulation can be attributed to reconsolidation interference (7)(8)(9)(10)(11)(12)(13)(14). In addition, there has been a considerable amount of failures to conceptually or exactly replicate previously published studies that appeared to demonstrate memory reconsolidation (15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25) and reconsolidation theory presently cannot illuminate which factors explain those negative results.…”

“…Although it has been acknowledged that reverse inference can be useful for scientific progress by suggesting novel hypotheses that can then be tested empirically, such inferences are only acceptable if the observation can occur if and only if the process of interest is engaged (27,40). This implies that reminder-dependent behavioral effects cannot be equated to the presence of reconsolidation interference per se (7,8,11). In addition, it should be acknowledged that behavioral studies can never prove the occurrence of a reconsolidation process, so caution is always required when making statements related to reconsolidation.…”