Pharmacological stimulation of infralimbic cortex after fear conditioning facilitates subsequent fear extinction

The infralimbic (IL) division of the medial prefrontal cortex (mPFC) is a crucial site for the extinction of conditioned fear memories in rodents. Recent work suggests that neuronal plasticity in the IL that occurs during (or soon after) fear conditioning enables subsequent IL-dependent extinction learning. We therefore hypothesized that pharmacological activation of the IL after fear conditioning would promote the extinction of conditioned fear. To test this hypothesis, we characterized the effects of post-conditioning infusions of the GABA_A receptor antagonist, picrotoxin, into the IL on the extinction of auditory conditioned freezing in male and female rats. In four experiments, we found that picrotoxin injections performed immediately, 24 h, or 13 days after fear conditioning reduced conditioned freezing to the auditory conditioned stimulus (CS) during both extinction training and extinction retrieval; this effect was observed up to two weeks after picrotoxin infusions. Interestingly, inhibiting protein synthesis inhibition in the IL immediately after fear conditioning prevented the inhibition of freezing by picrotoxin injected 24 h later. Our data suggest that the IL encodes an inhibitory memory during the consolidation of fear conditioning that is necessary for future fear suppression.