Role of the mPFC-Amygdala Circuit in Fear Extinction

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DESCRIPTION (provided by applicant): The goal of the proposed work is to elucidate the mechanisms underlying extinction of conditioned fear. Since extinction is widely used as a model for the treatment of anxiety disorders such as Post Traumatic Stress Disorder (PTSD), understanding its neural correlates will undoubtedly be beneficial to public health. Cortical influence over the amygdala is known to be inhibitory and [to] suppress conditioned fear, thus serving as the model structure for inhibitory control of amygdala output. The medial prefrontal cortex (mPFC) can inhibit the central nucleus of the amygdala (CEm), which is the main output projecting to downstream targets to produce a fearful response. We will test a model which posits that mPFC-mediated inhibition in the CEm can occur via its projection to small groups of GABAergic cells in the amygdala (the intercalated cell masses (ITCs)), which then project to and inhibit the CEm. ITCs will be lesioned by microinjections of saporin conjugated to an agonist of the mu-opioid receptor (which they abundantly express) and fear conditioning and its extinction will be tested. Electrophysiological recordings will determine whether the lesion has affected the inhibitory drive that the mPFC is known to exert on amygdala output.