Electrolytic lesions of the medial prefrontal cortex do not interfere with long-term memory of extinction of conditioned fear.

Lesion studies indicate that rats without the medial prefrontal cortex (mPFC) have difficulty recalling fear extinction acquired the previous day. Several electrophysiological studies have also supported this observation by demonstrating that extinction-related increases in neuronal activity in the mPFC participate in expression of fear extinction. However, a more recent study has shown that fear extinction can be recalled, in certain circumstances, without mPFC potentiation, suggesting contribution of other circuits. Here, we examined this possibility in rats that were subjected to auditory fear conditioning, extinction training, and extinction retention test 7 d later. Electrolytic lesions were made in the mPFC, the motor cortex (MO), the dorsal septum (SEP), or the mediodorsal thalamus (MD), because of their potential participation in conditioned fear inhibition; combined lesions including the mPFC with the MO, SEP, or MD were also made. The lesions were made either 1 wk before conditioning or 1 d after extinction training. All rats normally extinguished their conditioned freezing behavior during extinction training and did not display any return of this behavior during the retention test. These data reveal that the mPFC is not required for the acquisition, the expression, or the retrieval of extinction memories but do not exclude the possibility that the mPFC normally participates in these processes.