849. To avoid or not to avoid? Prefrontal integration of cortical inputs modulates extinction of avoidance

Abstract

Abstract Background The medial prefrontal cortex (mPFC) has a well-established role in extinction learning, triggering plasticity and cellular inhibition via projections to the amygdala. Simple behavioral models such auditory threat (fear) conditioning demonstrate how the infralimbic (IL) mPFC inhibits amygdala output during extinction learning, which is a key component of cognitive behavioral therapies for anxiety disorders. Aims & Objectives A simple modification of threat conditioning, in which a platform allows the rat to avoid the shock, permits the study of active avoidance decisions, where the animal must integrate threat with the pursuit of rewards. We aimed to uncover the circuits involved in active avoidance and its extinction. Method Using a combination of pharmacological interventions, neural recordings, and optogenetic tools, we studied the involvement of the prelimbic mPFC (PL), amygdala, and ventral striatum in rats engaged in platform-mediated avoidance. Results We demonstrate that the PL is crucial for suppressing avoidance behavior during extinction learning. The PL integrates contextual and emotional information from hippocampus and orbitofrontal cortex, and modulates behavioral responses by projecting to the ventral striatum, a region involved in action selection and motivation. Discussion & Conclusions These findings identify a key neural pathway that could be targeted to reduce pathological avoidance in anxiety-related condition such as PTSD and OCD.