221. Investigation of the neural circuitry underlying the extinction of inhibitory avoidance memory in mice
Abstract
Abstract Background The inhibitory avoidance (IA) task is widely employed as a translational preclinical model for aversive memory and post-traumatic stress disorder (PTSD). IA paradigms recapitulate core PTSD-like phenotypes, including persistence, context-specific avoidance and resistance to extinction. However, the neural circuits governing IA memory extinction remain incompletely defined. Aims & Objectives Previous studies have implicated an infralimbic cortex (IL)–paraventricular thalamus (PVT)–central amygdala (CeL) pathway in extinction-related processes. We hypothesized that IA memory extinction would engage this circuit, reflected by increased c-FOS expression within IL–PVT–CeL nodes during extinction retrieval. Method Mice received IA training on Day 1 using a single footshock (0.2 mA, 3 s). On Day 2, animals were assigned to one of three conditions: Home Cage (HC), Extinction (Ext; 10-min re-exposure), or Reconsolidation (Rec; 10-s re-exposure). On Day 3, all mice underwent retrieval testing followed by perfusion 90 min later for immunohistochemical analysis. Results Ext mice exhibited significantly shorter latencies to enter the dark compartment compared with Rec and HC mice, confirming successful extinction learning. At the neural level, c-FOS expression in the PVT was significantly elevated in Ext mice relative to Rec mice, supporting a role for the IL–PVT–CeL circuit in IA extinction. Discussion & Conclusions These findings identify the PVT as a potential hub for prefrontal–amygdala interactions during extinction. Ongoing studies using chemogenetic inhibition of this pathway aim to determine whether circuit disruption attenuates IA extinction expression. By delineating the neural circuitry supporting IA memory extinction, this work aims to facilitate the identification and evaluation of candidate therapeutics targeting pathological avoidance and impaired extinction processes characteristic of PTSD.