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

Wei Chen,Shaochen Zhao,Junjiao Li,Min Fan,Xifu Zheng,Liang Xu

doi:10.3389/fnbeh.2020.598924

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.

Highlights

Memories with extreme emotional connotations serve a pathogenic role in diverse psychiatric disorders, such as posttraumatic stress disorder (PTSD), as well as phobias (Beckers and Kindt, 2017; Chen et al, 2020)
We found that applied extinction training 10 min postretrieval did not prevent fear-potentiated startle, as well as skin conductance responses in spontaneous recovery, and reinstatement tests, when the parameters of acquisition and retrieval were identical
Retrieval-extinction decreased spontaneous recovery (FPS and skin conductance response (SCR)) and reinstatement of fear (FPS) when a mismatch occurred between initial training and memory retrieval (PE)

Summary

Introduction

Memories with extreme emotional connotations serve a pathogenic role in diverse psychiatric disorders, such as posttraumatic stress disorder (PTSD), as well as phobias (Beckers and Kindt, 2017; Chen et al, 2020). After retrieval, consolidated memory enters a transient labile period, in which it might be vulnerable to amnestic interventions and require de novo protein synthesis for re-stabilization to persist. During this window period, memory can be modified by protein synthesis inhibitors (e.g., anisomycin) or beta receptor antagonists (e.g., propranolol) (Nader et al, 2000; Debiec and Ledoux, 2004; Kindt et al, 2009). In the retrieval-extinction procedure, an isolated retrieval trial is presented to destabilize consolidated memory This is followed by introduction of extinction training for updating the memory in the reconsolidation period in place of generating a second memory trace, which competes for expression. More work is required before the approach is applied in clinical interventions

Methods

Results

Conclusion