Inactivation of the Medial Prefrontal Cortex Interferes with the Expression But Not the Acquisition of Differential Fear Conditioning in Rats

The medial prefrontal cortex (mPFC) has been implicated in the processing of emotionally significant stimuli, particularly the inhibition of inappropriate responses. We examined the role of the mPFC in regulation of fear responses using a differential fear conditioning procedure in which the excitatory conditioned stimulus (CS+) was paired with an aversive footshock and intermixed with the inhibitory conditioned stimulus (CS-). In the first experiment, using rats as subjects, muscimol, a gamma-amino-butyric acid type A (GABAA) receptor agonist, or artificial cerebrospinal fluid (aCSF) was infused intracranially into the mPFC across three conditioning sessions. Twenty-four hours after the last conditioning session, freezing response of the rats was tested in a drug-free state. Neither the muscimol nor the aCSF infusion had any effect on differential responding. In the second experiment, the same experimental procedure was used except that the infusion was made before the testing session rather than the conditioning sessions. The results showed that muscimol infusion impaired differential responding: the level of freezing to CS- was indiscriminable from that to CS+. Taken together, these results suggest that the mPFC is responsible for the regulation of fear response by inhibiting inappropriate fear expressions.