Role of Amygdala-Infralimbic Cortex Circuitry in Glucocorticoid-induced Facilitation of Auditory Fear Memory Extinction

Introduction: The basolateral amygdala (BLA) and infralimbic area (IL) of the medial prefrontal cortex (mPFC) are two interconnected brain structures that mediate both fear memory expression and extinction. Besides the well-known role of the BLA in the acquisition and expression of fear memory, projections from IL to BLA inhibit fear expression and have a critical role in fear extinction. However, the details of IL-BLA interaction have remained unclear. Here, we investigated the role of functional reciprocal interactions between BLA and IL in mediating fear memory extinction. Methods: Using lidocaine (LID), male rats underwent unilateral or bilateral inactivation of the BLA and then unilateral intra-IL infusion of corticosterone (CORT) prior to extinction training of the auditory fear conditioning paradigm. Freezing behavior was reported as an index for conditioned fear. Infusions were performed before the extinction training, allowing us to examine the effects on fear expression and further extinction memory. Experiments 1-3 investigated the effects of left or right infusion of CORT into IL and LID unilaterally into BLA on fear memory extinction. Results: Intra-IL infusion of CORT in the right hemisphere reduced freezing behavior when administrated before the extinction training. Auditory fear memory extinction was impaired by asymmetric inactivation of BLA and CORT infusion in the right IL; however, the same effect was not observed with symmetric inactivation of BLA.  Conclusion: IL-BLA neural circuit may provide additional evidence for the contribution of this circuit to auditory fear extinction. This study demonstrates dissociable roles for right or left BLA in subserving the auditory fear extinction. Our finding also raises the possibility that left BLA-IL circuitry may mediate auditory fear memory extinction via underlying mechanisms. However, further research is required in this area.