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The role of ventromedial prefrontal cortex in the recovery of extinguished fear - PubMed

  • ️Sat Jan 01 2000

The role of ventromedial prefrontal cortex in the recovery of extinguished fear

G J Quirk et al. J Neurosci. 2000.

Abstract

Conditioned fear responses to a tone paired with footshock extinguish when the tone is presented repeatedly in the absence of shock. Rather than erase the tone-shock association, extinction is thought to involve new learning accompanied by inhibition of conditioned responding. Despite much interest in extinction from a clinical perspective, little is known about the neural circuits that are involved. Although the prefrontal cortex has a well established role in the inhibition of inappropriate behaviors, previous reports have disagreed as to the role of the ventromedial prefrontal cortex (vmPFC) in extinction. We have reexamined the effects of electrolytic vmPFC lesions made before training on the acquisition, extinction, and recovery of conditioned fear responses in a 2 d experiment. On Day 1 vmPFC lesions had no effect on acquisition or extinction of conditioned freezing and suppression of bar pressing. On Day 2 sham rats recovered only 27% of their acquired freezing, whereas vmPFC-lesioned rats recovered 86%, which was indistinguishable from a control group that never received extinction. The high recovery in lesioned rats could not be attributed to decreased motivation or altered sensitivity to footshock. vmPFC lesions that spared the caudal infralimbic (IL) nucleus had no effect. Thus, the vmPFC (particularly the IL nucleus) is not necessary for expression of extinction, but it is necessary for the recall of extinction learning after a long delay. These data suggest a role of the vmPFC in consolidation of extinction learning or the recall of contexts in which extinction took place.

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Figures

Fig. 1.
Fig. 1.

A diagram showing the extent of lesions in ventromedial prefrontal cortex (vmPFC). The largest (outline) and smallest (filled) lesions are shown for each level. A, The vmPFC-inclusive group showed >70% destruction of the infralimbic nucleus at all levels (n = 11). B, The vmPFC-rostral group spared some or all of the IL nucleus caudally (n = 6). Cg1, Anterior cingulate cortex; DP,dorsal peduncular nucleus; IL, infralimbic nucleus;LS, lateral septum; MO, medial orbital cortex; M2, secondary motor cortex; PrL,prelimbic cortex; VO, ventral orbital cortex. Numbers indicate location anterior to bregma (mm). Modified from Paxinos and Watson (1998).

Fig. 2.
Fig. 2.

Average freezing (A) and suppression (B) values for each trial of the experiment. A habituation phase (tones alone) was followed by a conditioning phase (tones plus shocks) and an extinction phase (tones alone). Freezing is expressed as a percentage of the 30 sec tone spent motionless. Suppression of bar pressing to the tone was expressed as a suppression ratio, which compared pretone rates with tone rates (see Materials and Methods). A ratio of 1.0 indicated maximal suppression to the tone, whereas 0 indicated no suppression. No difference in fear responses was found between the groups on Day 1. However, vmPFC-i animals showed higher recovery of the fear responses at the beginning of Day 2. Empty circle, Sham-operated; filled diamond, vmPFC-i lesion. In this and all subsequent figures the error bars indicate SEM.

Fig. 3.
Fig. 3.

Average freezing (A) and suppression (B) values for two-trial blocks on Day 1 and Day 2 shown for sham-operated (empty bars), vmPFC-i (filled bars), and vmPFC-r (hatched bars) groups. Note the high recovery of fear responses to the tone on Day 2 in the vmPFC-i group, but not in the vmPFC-r group. ANOVA indicated that the vmPFC-i group was significantly different from the sham group only on Day 2 (p < 0.001).

Fig. 4.
Fig. 4.

Recovery of extinguished freezing (A) and suppression (B) responses on Day 2, expressed as a percentage of fear response acquired on Day 1. Four groups are shown: extinction-naïve, sham-operated, vmPFC-i (PFC-i), and vmPFC-r (PFC-r). An asterisk indicates that the vmPFC-i group was significantly higher than the sham group (p < 0.001), but not significantly different from the extinction-naïve group (p > 0.05).

Fig. 5.
Fig. 5.

Extinction trials on Day 2 for vmPFC-i and extinction-naive groups, shown for freezing (A) and suppression (B). Despite complete recovery of fear responses on Day 2, vmPFC-i rats showed savings in their rate of extinction, suggesting some retention of extinction learning from Day 1.

Fig. 6.
Fig. 6.

Reinstatement of freezing to the tone.A, Sham, vmPFC-i, and vmPFC-r groups increased their freezing to the tone after two unsignaled shocks. B, Freezing in the pretone period was subtracted from freezing during the tone for sham and sham-unpaired groups. Shams showed significant tone-induced freezing that was greater than pretone freezing, but sham-unpaired did not, indicating that increased freezing was not attributable to a sensitization effect.

Fig. 7.
Fig. 7.

Pretone press rates and footshock sensitivity.A, Spontaneous press rates during the 60 sec before tone onset for sham and vmPFC-i groups. Blocks of five trials during the extinction sessions of Day 1 and Day 2 are shown. Press rates did not differ between groups or across trials. B, Footshock response thresholds for sham and vmPFC-i groups. vmPFC-i lesions did not alter sensitivity to footshock.

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