Activity in prelimbic cortex is necessary for the expression of learned, but not innate, fears

The amygdala has long been considered to be both necessary and sufficient for classical fear conditioning, but recent evidence suggests that the medial prefrontal cortex (mPFC) may also be involved. The prelimbic (PL) subregion of mPFC projects to the amygdala, and neurons in PL show fear-related increases in activity. It is unknown, however, whether PL activity is necessary for expression of learned fears, expression of innate fears, or the learning of fear associations. To address this, we used the sodium channel blocker tetrodotoxin to inactivate PL during fear learning or expression. Inactivation of PL reduced freezing to both a tone and a context that had been previously paired with footshock (learned fear) but had no effect on freezing to a cat (innate fear). Inactivation of PL before conditioning, however, did not prevent the formation of auditory or contextual fear memories. Thus, activity in PL is critical for the expression, but not the acquisition, of learned fears. We suggest that PL integrates information from auditory and contextual inputs and regulates expression of fear memories via projections to the basal nucleus of the amygdala.