Learning-Induced Changes in mPFC–BLA Connections After Fear Conditioning, Extinction, and Reinstatement of Fear

Abstract

The neural circuit linking the medial prefrontal cortex (mPFC) and the basolateral amygdala (BLA) has crucial roles in both the acquisition and the extinction of fear. However, the mechanism by which this circuit encodes fear and extinction remains unknown. In this study, we monitored changes in the magnitude of evoked field potentials (EFPs) in the mPFC-BLA and BLA-mPFC pathways following auditory fear conditioning and extinction, in freely moving rats. We report that extinction of fear is mediated by depression of the EFPs in the mPFC-BLA and by potentiation in the reciprocal pathway of BLA-mPFC. Interestingly, reinstatement of fear was associated with recovery of freezing and with reversal of the changes in EFPs that were observed following extinction in both pathways. The findings indicate that the mPFC-BLA circuit expresses differential changes following fear and extinction and point to dynamic and plastic changes underlying fear, extinction, and reinstatement. Manipulations targeting these different types of plasticity could constitute a therapeutic tool for the treatment of anxiety disorders.

Vagus nerve stimulation reduces cocaine seeking and alters plasticity in the extinction network

“…This suggests differences in the ability to induce plasticity in the BLA during each of the phases of the self-administration/extinction paradigm, that are caused by either the drug itself, learned cue-reward associations, or extinction learning. This is again similar to what is seen in the IL BLA pathway during fear conditioning and extinction from conditioned fear (Vouimba and Maroun 2011). There, the response in the BLA increases after fear conditioning and remains elevated unless subjects undergo extinction, at which point the response becomes smaller than the baseline response.…”

Differences in Stress-Induced Changes in Extinction and Prefrontal Plasticity in Postweanling and Adult Animals

“…In the PW animal, only the animals that underwent extinction expressed LTP, hinting that potentiation does not occur during extinction training, unlike our previous report on adult animals (57). These results also support that stress-induced extinction alterations (and possibly other forms of extinction as well) are mediated by different mechanisms in the two age groups.…”

“…Similarly, in the adult animal, the group that underwent extinction training did not show LTP following TBS, and in contrast, the EXT 1 EP group that showed impaired extinction had high levels of LTP. Studies have shown an overlap of mechanisms mediating HFS-LTP and training-induced synaptic potentiation in relevant brain structures mediating these types of learning [e.g., (39)(40)(41)56,57)]. Importantly, potentiation induced by the behavioral training occluded the subsequent induction of LTP by electrical HFS (39)(40)(41).…”

Exposure therapy triggers lasting reorganization of neural fear processing

“…These neurophysiological processes include immediate increases in prefrontal activity in conjunction with decreases in activity of the amygdala, as well as a consolidation process that eventually allows decreased amygdala and limbic responsivity to occur independently from PFC involvement. Although neural inhibition is difficult to demonstrate in human studies, our findings show altered neural processing patterns in regions homologous to PFC-amygdala inhibitory circuitry in rodents that have undergone extinction (26). While the dlPFC subregion identified in this study does not project directly to amygdala (27), it may inhibit amygdala via projections to additional regions, particularly vmPFC-a region implicated in fearextinction recall and considered a homolog of extinction-sensitive infralimbic structures in rodents (14,15,27,28).…”