Contrasting patterns of ERK activation in the tail of the striatum in response to aversive and rewarding signals

The caudal part of the striatum, also named the tail of the striatum (TS), defines a fourth striatal domain. Determining whether rewarding, aversive and salient stimuli regulate the activity of striatal spiny projections neurons (SPNs) of the TS is therefore of a paramount importance to understand its functions, which remain largely elusive. Taking advantage of genetically encoded biosensors (AKAR3) to record PKA signals and by analyzing the distribution of D1R- and D2R/A2aR-SPNs in the TS, we characterized three evolutionary highly conserved subterritories: a D2R/A2aR-lacking area, a D1R/D2-SPNs-enriched and an D1R/D2R-intermingled area. The analysis of ERK phosphorylation in these TS subterritories in response to distinct appetitive, aversive and pharmacological stimuli revealed that SPNs of the TS are not recruited by stimuli triggering innate or learned avoidance responses, fasting, satiety or palatable signals. In contrast, D1R-SPNs of the intermingled and D2R/A2AR-lacking areas are strongly activated by both direct stimulation of D1R and psychostimulant drugs (d-amphetamine, cocaine, MDMA or methylphenidate), but not by hallucinogens. Finally, a similar pattern of ERK activation was observed by blocking selectively dopamine reuptake. Together, our results reveal that the caudal TS might participate in the processing of specific reward signals.