Extinction and Retrieval + Extinction of Conditioned Fear Differentially Activate Medial Prefrontal Cortex and Amygdala in Rats

Abstract

Pairing a previously neutral conditioned stimulus (CS; e.g., a tone) to an aversive unconditioned stimulus (US; e.g., a footshock) leads to associative learning such that the tone alone comes to elicit a conditioned response (e.g., freezing). We have previously shown that an extinction session that occurs within the reconsolidation window (termed retrieval + extinction) attenuates fear responding and prevents the return of fear in Pavlovian fear conditioning (Monfils et al., 2009). To date, the mechanisms that explain the different behavioral outcomes between standard extinction and retrieval + extinction remain poorly understood. Here we sought to examine the differential temporal engagement of specific neural systems by these two approaches using Arc catFISH (cellular compartment analysis of temporal activity using fluorescence in situ hybridization (FISH)). Our results demonstrate that extinction and retrieval + extinction lead to differential patterns of expression, suggesting that they engage different networks. These findings provide insight into the neural mechanisms that allow extinction during reconsolidation to prevent the return of fear in rodents.

Reconsolidation-Extinction Interactions in Fear Memory Attenuation: The Role of Inter-Trial Interval Variability

“…We do not believe this could be the case. Recent studies have indeed shown that post-retrieval extinction engages mechanisms that are distinct from “standard” extinction (Monfils et al, 2009; Clem and Huganir, 2010; Rao-Ruiz et al, 2011; Tedesco et al, 2014; Lee et al, 2016). One explanation of memory updating is that an experience that both evokes a memory for and greatly resembles a previous experience (i.e., possess the same latent causes) is likely to be integrated with the previous memory.…”

Post-retrieval extinction in adolescence prevents return of juvenile fear

“…It is especially interesting that adolescent retrieval+ extinction would prevent the recovery of juvenile fears when adult retrieval+extinction on fear memories of similar temporal age fails to attenuate fear (Clem and Huganir 2010;Gräff et al 2014). At the molecular level, retrieval+extinction of a fear memory targets synaptic plasticity within the lateral amygdala where it is hypothesized to destabilize the original memory trace (Monfils et al 2009;Clem and Huganir 2010) by inducing a reconsolidation-like process in the LA, IL, and PRL (Tedesco et al 2014), and engages a mechanism distinct from that involved in standard extinction (Lee et al 2015). This suggests that successful fear reduction with the retrieval+extinction procedure requires destabilization of the memory trace in the LA paired with the incorporation of new information from the PFC.…”

The Computational Nature of Memory Modification

“…Furthermore, the Monfils-Schiller paradigm has been shown to induce neural modifications that are distinct from standard extinction (H. J. Lee, Haberman, Roquet, & Monfils, 2015;Tedesco, Roquet, DeMis, Chiamulera, & Monfils, 2014).…”