Extended Data Fig. 10: Model of DA action on PKA activity of SPNs.

Overview of DA action on SPN PKA activity. Top, when DAN activity increases in response to a reward, reward predictive cue or optogenetic activation of DANs, more DA is released from DAN terminals in the NAc. This increase in DA level allows DA to bind to D1R, which increases the activity of adenylyl cyclase, the level of cAMP and—ultimately—the activity of PKA in D1R-SPNs. By contrast, the increase in DA level has a minimal effect on D2R, which is occupied by the basal level of DA. Bottom, when DAN activity decreases in response to a reward omission or optogenetic inhibition of DANs, DA release from DAN terminals in the NAc decreases below the baseline. This decrease in DA level has a minimal effect on D1R, which is not occupied by the basal DA. By contrast, the decrease in DA level allows the basal DA to unbind from D2R, which disinhibits PKA activity in D2R-SPNs.