Figure 1.

Dopaminergic modulation of the neural circuitry underlying fear extinction. Schematic of the three major projections of the ventral tegmental area (VTA) dopamine (DA) neurons likely involved in fear extinction are shown. BLA, basolateral amygdala; EPE, extinction prediction error; IL, infralimbic cortex; ITCs, intercalated cell masses (dm: dorsomedial, vm: ventromedial); LC, locus coeruleus; NA, noradrenalin; NAc, nucleus accumbens. Question marks (?) indicate possible DAergic projections mediating fear extinction. The involvement of these projections in extinction remains to be tested. (A) A subset of VTA DA neurons encodes an EPE signal that is necessary to initiate fear extinction learning. The projection target of EPE encoding DA neurons is currently unknown. NAc constitutes an ideal candidate however the exact subregion of NAc receiving the EPE signal remains to be determined. (B) Activation of DA receptors in the BLA mediates the acquisition of fear extinction memories. However, the source of DA input to the amygdala during extinction has not directly been demonstrated. Whether VTA DA projections to the BLA and also likely to dmITCs, are involved in fear extinction is an important outstanding question. (C) DA is crucial for the consolidation of extinction memories in the IL. The source of DA input to IL during fear extinction has remained elusive, however, IL receives its main DA input from the VTA and IL-projecting VTA DA neurons are thus plausible candidates. However, recent studies suggest that this DA projection is pro-aversive; and thus, DA released from other sources, such as NA neurons located in the LC might be more likely to mediate fear extinction.