P.2.014 - The medial pre-frontal cortex plays a distinctive role in extinction of both recent and remote fear in post weanling rats

Abstract

Contextual fear conditioning (CFC) and conditioned odor aversion (COA) are behavioral paradigms based on associations between neutral conditioned stimuli (CS) with aversive unconditioned stimuli (US). Without extinction training fear and aversive memories can last for a life time. In CFC, the infralimbic subregion of the medial prefrontal cortex (IL-mPFC) was established to have a key role in consolidation and recall of recent (24-48 hrs) fear extinction memory. Recent and remote memories are both considered as long-term memories and they were hypothesized to be supported by different brain circuits. We previously provided evidence that the IL is similarly required for extinction consolidation of recent and remote (28 days) fear memory. However, in COA, the IL was only involved in extinction consolidation of recent, but not remote memory [1]. Based on our previous findings suggesting that post-weanling (PW; PND27) and adult animals have different mechanisms of extinction [2], in this study we aimed to explore the role of the IL in recent and remote CFC and COA in the PW animal. Further, we aimed to compare the mechanisms of extinction, the involvement of IL-mPFC in the PW animal and to address whether similar mechanisms are engaged in the two types of memories. For the purpose, we used behavioral, pharmacological and molecular tools to address these questions. PW rats were fear or COA conditioned, and extinction was examined in recent or remote time points. Lidocaine was microinjected into the IL before the retrieval (T1) and Anisomycin was microinjected after T1. In both experiments the control groups were microinjected with saline. Western blot analysis was performed on samples collected from the IL at different time points. Results were presented as mean ± S.E.M. For statistical analysis, independent t-test, One Way ANOVA and ANOVA for repeated measures tests were used as indicated. Our results show that reversible inactivation before retrieval or protein synthesis inhibition after retrieval both impaired the recent CFC extinction and resulted in enhanced freezing levels. In contrast, in remote CFC only the inactivation of the IL before the remote retrieval reduced freezing over the testing days, suggesting attenuation of fear memory. However, the same treatments did not affect the extinction of remote and recent COA. Furthermore, only remote retrieval induced c-Fos activation in the IL following both paradigms as determined by western blot analysis. These results indicate differential engagement of the IL in the consolidation of recent and remote extinction. Altogether, these results point to an important difference between CFC and COA regarding the role of the IL in the extinction and further confirm the differences of the engagement of the IL in extinction of aversive memories in PW and adult animals [1]. Since the PW stage of development is roughly equivalent to early human childhood, studying aversive memory at this stage can give us more insight to the treatment of anxiety disorders in children.