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

Abstract

All custom-made materials will be shared upon reasonable request. Running title: ERK, dopamine and the caudal striatumKeywords: striatum, dopamine, ERK, D1R, D2R, psychostimulants ERK, dopamine and the caudal striatum 2 AbstractThe 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 paramount importance to understand its functions, which remain largely elusive.Taking advantage of genetically encoded biosensors (A-kinase activity reporter 3, AKAR3) to record PKA signals and by analyzing the distribution of dopamine D1Rand D2R-SPNs in the TS, we characterized three subterritories: a D2R/A2aR-lacking, a D1R/D2R-intermingled and a D1R/D2R-SPNs-enriched area (corresponding to the amygdalostriatal transition). In addition, we provide evidence that the distribution of D1R-and D2R-SPNs in the TS is evolutionarily conserved (mouse, rat, gerbil). The in vivo analysis of extracellular signal-regulated kinase (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 aversive responses, fasting, satiety or palatable signals whereas a reduction in ERK phosphorylation occurred following learned avoidance. In contrast, D1R-SPNs of the intermingled and D2R/A2aR-lacking areas were strongly activated by both D1R agonists 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 and discrete aversive stimuli.ERK, dopamine and the caudal striatum 3

Conservation of the direct and indirect pathways dichotomy in mouse caudal striatum with uneven distribution of dopamine receptor D1- and D2-expressing neurons

“…The uneven distribution was also observed in ICR mice (11 weeks; N = 3). The uneven distribution of D1R and D2R were also found in the cStr of Wistar (N = 3, Figure 7C) and Long-Evans rats (N = 3, Figure 7D), as reported previously (Gangarossa et al, 2019). As the same as mice, D2R-poor zone was always located at the most caudal part of the striatum, and D1Rpoor zone was rostral to and medial to D2R-poor zone, although the appearance (shape and size) was bit different from those in mice.…”

“…In transgenic mice, the uneven distribution of D1R and D2R expressing neurons in the cStr (Gangarossa et al, 2013(Gangarossa et al, , 2019Miyamoto et al, 2019). The present study with wild type C57BL/6J mice also showed the uneven distribution of D1R and D2R expressing neurons in cStr and the coordinates of the boundary of D1R-and D2R-poor zones appear to be coincidence (Figures 1A-C).…”

Identification of an endocannabinoid gut-brain vagal mechanism controlling food reward and energy homeostasis

“…Here, we investigated whether bingeing modulated the DA-associated signaling machinery. Thus, we used the activation (phosphorylation) of the ribosomal protein S6 (rpS6) and the extracellular signal-regulated kinases (ERK) as functional readouts of DA-dependent molecular activity (Gangarossa et al, 2013a, 2013b, 2019; Valjent et al, 2019). We first investigated such molecular activations in bingeing mice before and after reward-diet consumption ( Figure 3A ) in the DS and NAc ( Figure 3B ).…”

Selection of active defensive behaviors relies on extended amygdala dopamine D2 receptors

“…The experiment was carried out in a fear conditioning apparatus (Imetronic, Pessac, France) 25 . It consists of two soundproof boxes with different contextual configurations.…”

“…The experiment was carried out in a soundproof shuttle box (Imetronic, Pessac, France)25 . The apparatus is made of two equal compartments (20 x 20 cm) separated by an opened door.…”