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Destabilizing Different Strengths of Fear Memories Requires Different Degrees of Prediction Error During Retrieval.

ABSTRACT: Reactivation of consolidated memories can induce a labile period, in which these reactivated memories might be susceptible to change and need reconsolidation. Prediction error (PE) has been recognized as a necessary boundary condition for memory destabilization. Moreover, memory strength is also widely accepted as an essential boundary condition to destabilize fear memory. This study investigated whether different strengths of conditioned fear memories require different degrees of PE during memory reactivation in order for the memories to become destabilized. Here, we assessed the fear-potentiated startle and skin conductance response, using the post-retrieval extinction procedure. A violation of expectancy (PE) was induced during retrieval to reactivate enhanced (unpredictable-shock) or ordinary (predictable-shock) fear memories that were established the day before. Results showed that a PE retrieval before extinction can prevent the return of predictable-shock fear memory but cannot prevent the return of unpredictable-shock fear memory, indicating that a single PE is insufficient to destabilize enhanced fear memory. Therefore, we further investigated whether increasing the degree of PE could destabilize enhanced fear memory using different retrieval strategies (multiple PE retrieval and unreinforced CS retrieval). We found that spontaneous recovery of enhanced fear memory was prevented in both retrieval strategies, but reinstatement was only prevented in the multiple PE retrieval group, suggesting that a larger amount of PE is needed to destabilize enhanced fear memory. The findings suggest that behavioral updating during destabilization requires PE, and the degree of PE needed to induce memory destabilization during memory retrieval depends on the strength of fear memory. The study indicates that memory reconsolidation inference can be used to destabilize stronger memories, and the findings shed lights on the treatment of posttraumatic stress disorders and anxiety disorders.

SUBMITTER: Chen W

PROVIDER: S-EPMC7820768 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Destabilizing Different Strengths of Fear Memories Requires Different Degrees of Prediction Error During Retrieval.

Chen Wei W Li Junjiao J Xu Liang L Zhao Shaochen S Fan Min M Zheng Xifu X

Frontiers in behavioral neuroscience 20210108

Reactivation of consolidated memories can induce a labile period, in which these reactivated memories might be susceptible to change and need reconsolidation. Prediction error (PE) has been recognized as a necessary boundary condition for memory destabilization. Moreover, memory strength is also widely accepted as an essential boundary condition to destabilize fear memory. This study investigated whether different strengths of conditioned fear memories require different degrees of PE during memo ...[more]

PMID: 33488366

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Project description:BackgroundLong-term memory formation is generally assumed to involve the permanent storage of recently acquired memories, making them relatively insensitive to disruption, a process referred to as memory consolidation. However, when retrieved under specific circumstances, consolidated fear memories are thought to return to a labile state, thereby opening a window for modification (e.g., attenuation) of the memory. Several interventions during a critical time frame after this destabilization seem to be able to alter the retrieved memory, for example by pharmacologically interfering with the restabilization process, either by direct protein synthesis inhibition or indirectly, using drugs that can be safely administered in patients (e.g., propranolol). Here, we find that, contrary to expectations, systemic pharmacological manipulations in auditory fear-conditioned rats do not lead to drug-induced post-retrieval amnesia.ResultsIn a series of well-powered auditory fear conditioning experiments (four with propranolol, 10 mg/kg, two with rapamycin, 20-40 mg/kg, one with anisomycin, 150 mg/kg and cycloheximide, 1.5 mg/kg), we found no evidence for reduced cued fear memory expression during a drug-free test in adult male Sprague-Dawley rats that had previously received a systemic drug injection upon retrieval of the tone fear memory. All experiments used standard fear conditioning and reactivation procedures with freezing as the behavioral read-out (conceptual or exact replications of published reports) and common pharmacological agents. Additional tests confirmed that the applied drug doses and administration routes were effective in inducing their conventional effects on expression of fear (propranolol, acutely), body weight (rapamycin, anisomycin, cycloheximide), and consolidation of extinction memories (cycloheximide).ConclusionsIn contrast with previously published studies, we did not find evidence for drug-induced post-retrieval amnesia, underlining that this effect, as well as its clinical applicability, may be considerably more constrained and less readily reproduced than what the current literature would suggest.

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Destabilizing Different Strengths of Fear Memories Requires Different Degrees of Prediction Error During Retrieval.

Publications

Destabilizing Different Strengths of Fear Memories Requires Different Degrees of Prediction Error During Retrieval.

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