Prefrontal mechanisms in extinction of conditioned fear

Interest in the medial prefrontal cortex (mPFC) as a source of behavioral inhibition has increased with the mounting evidence for a functional role of the mPFC in extinction of conditioned fear. In fear extinction, a tone-conditioned stimulus (CS) previously paired with a footshock is presented repeatedly in the absence of footshock, causing fear responses to diminish. Here, we review converging evidence from different laboratories implicating the mPFC in memory circuits for fear extinction: (1) lesions of mPFC impair recall of extinction under various conditions, (2) extinction potentiates mPFC physiological responses to the CS, (3) mPFC potentiation is correlated with extinction behavior, and (4) stimulation of mPFC strengthens extinction memory. These findings support Pavlov's original notion that extinction is new learning, rather than erasure of conditioning. In people suffering from posttraumatic stress disorder (PTSD), homologous areas of ventral mPFC show morphological and functional abnormalities, suggesting that extinction circuits are compromised in PTSD. Strategies for augmenting prefrontal function for clinical benefit are discussed.