Effects Of Electrolytic Lesion Of Prefrontal Subregions On Fear Extinction In Rats

Objectives: Extinction of fear conditioning in animals is an excellent model for the study of fear inhibition in humans, but the neural mechanisms of fear extinction has not yet been elucidated. However, most of the cumulated data on extinction is based on the classical predictable delay fear conditioning (PDC). Within the prefrontal cortex (PFC), recent evidence has demonstrated that the ventromedial (vmPFC) but not the ventrolateral (vlPFC) part of this region is a critical site of the neural circuits underlying extinction memory. On the basis of delay fear conditioning, we developed a modified unpredictable delay fear conditioning (UPDC) paradigm. Here, we examined the role of vmPFC and vlPFC in the extinction of PDC and UPDC.Methods: 1.Surgery: vmPFC-lesioned group The electrolytic lesion targeted the infralimbic cortex (IL) subdivisions of vmPFC. For sham-operated rats the electrode was lowered to a point just above the prelimbic cortex, but no current was passed. vlPFC-lesioned group The electrolytic lesion targeted vlPFC. Sham-operated rats received an identical surgical procedure with the exception of insertion of the electrode. 2. Fear conditioning and extinction: Behaviour procedure involved four training phases: habituation, fear conditioning, extinction training and extinction test. 9 d after the surgery rats received a fear conditioning session (PDC or UPDC). 24 and 48 hr after conditioning, rats received an extinction training session and an extinction test session, respectively. Percent freezing was assessed during all phases of training. 3. Locomotor activity: tested 9 d after the surgery. 4. Foot shock sensitivity: tested 12 d after the surgery. The rats received unsigned footshocks of increasing amplitude in conditioning chamber. Footshock stopped until three response thresholds appear: noticing, flinching, and vocalizing.Results:1. In the PDC task, vmPFC-lesioned group showed higher level of percent freezing than sham-operated group in the extinction test session, but there was no significant difference in freezing between the two groups in fear conditioning session and extinction training session. Two groups showed comparable rates of within-session extinction. However, there was no significant difference in freezing between vlPFC-lesioned group and sham-operated group in fear conditioning, extinction training, and extinction test session. 2. In the UPDC task, vmPFC-lesioned group showed higher level of percent freezing than sham-operated group in the extinction test session, but there was no significant difference in freezing between the two groups in fear conditioning session and extinction training session. Two groups showed comparable rates of within-session extinction. Equally, vlPFC-lesioned group showed higher level of percent freezing than sham-operated group in the extinction test session, but there was no significant difference in freezing between the two groups in fear conditioning session and extinction training session. Two groups showed comparable rates of within-session extinction. 3. There was no significant difference in locomotor activity between lesioned groups and their corresponding sham-operated groups tested 9 d after the surgery. 4. There was no significant difference in footshook sensitivity tested 12d after the surgery. 5. There was no significant difference in nonspecific freezing to the tone and context.Conclusion:vmPFC lesion impaired the extinction in both PDC and UPDC tasks, but vlPFC lesion only impaired the extinction in PDC tasks, and had no effect on the extinction in UPDC tasks.