Medial prefrontal cortex: multiple roles in fear and extinction

Anxiety disorders are among the most common mental health problems; deficits in extinction have been implicated as a possible risk factor for the development of these disorders. Fear extinction refers to the ability to adapt as situations change by learning to suppress a previously acquired fear. Attention is directed toward the medial prefrontal cortex (mPFC) and the interaction it has with the amygdala as this circuit has crucial roles in both the acquisition and the extinction of fear associations. Here, we review converging evidence from different laboratories pointing to multiple roles that the mPFC has in fear regulation. Research on rodents indicates opposing roles that the different subregions of the mPFC have in exciting and inhibiting fear. In addition, this review aims to survey the findings addressing the mechanisms by which the mPFC regulates fear. Data from our laboratory and others show that changes in plasticity in the mPFC could be one of the mechanisms mediating extinction of fear. Recent findings on rodents and nonhuman primates report that modifying plasticity in the mPFC alters fear and affects extinction, suggesting that targeting plasticity in the mPFC could constitute a therapeutic tool for the treatment of anxiety disorders.