Investigating the role of dopamine receptor- and parvalbumin-expressing cells in extinction of conditioned fear

•Extinction increased Fos+ and decreased D2R+ cells in the infralimbic cortex.•Fear retrieval increased Fos labeling of D2R+ cells in the prelimbic cortex.•Context exposure, retrieval, and extinction display overlapping neural activation. The present study examined the pattern of activation of neurons that express dopamine receptors 1 and 2 (D1R and D2R), and parvalbumin (PV) in mice that underwent extinction of a fear memory. Adult male transgenic mice expressing D1R or D2R tagged with green fluorescent protein (GFP) were conditioned with 6 tone-shock pairings. The following day they were randomly divided into one of four experimental groups: extinction, retrieval, context or handled. Extinction groups were exposed to 45 tone presentations, retrieval groups were exposed to 5 tone presentations and the context groups were exposed to the chamber without any tones. Ninety minutes following their assigned treatment, mice were perfused and brain tissue processed for Fos/GFP/PV immunohistochemistry. Quantification of immunoreactivity revealed that extinction resulted in changes in the infralimbic cortex including increased Fos expression and a decrease in the number of D2R+ cells compared to all other groups. Conversely, fear memory retrieval resulted in increased activation of D2R+ cells in the prelimbic cortex compared to all other groups. Additional changes were observed in the extinction and retrieval groups that were different to the handled group, but not to the context group, which highlights that there is overlapping neurocircuitry between extinction and retrieval of fear memory, as well as with context exposure. These results provide novel insights into the roles of specific dopamine receptor subtypes, which will be valuable for informing future research that aims to strengthen extinction learning via dopaminergic mechanisms.