Dopamine systems adaptation during acquisition and consolidation of a skill

Abstract

The striatum plays a key role in motor learning. Striatal function depends strongly on dopaminergic neurotransmission, but little is known about neuroadaptions of the dopamine system during striatal learning. Using an established task that allows differentiation between acquisition and consolidation of motor learning, we here investigate D1 and D2-like receptor binding and transcriptional levels after initial and long-term training of mice. We found profound reduction in D1 binding within the dorsomedial striatum (DMS) after the first training session on the accelerated rotarod and a progressive reduction in D2-like binding within the dorsolateral striatum (DLS) after extended training. Given that similar phase- and region-specific striatal neuroadaptations have been found also during learning of complex procedural tasks including habit formation and automatic responding, the here observed neurochemical alterations are important for our understanding of neuropsychiatric disorders that show a dysbalance in the function of striatal circuits, such as in addictive behaviors.

Keywords: dopamine receptors; gene expression; learning; neuroadaptation; receptor binding; rotarod; striatum.

Figure 1

Representative expression pattern of the dopaminergic neurotransmitter system in a mouse brain. (A) Schematic representation of the sampled areas for densitometric evaluation of the autoradiography and in situ hybridization experiments in a coronal section of a mouse brain. Bregma levels = +1 mm, +0.4 mm, −3.5 mm. AcbC: Accumbens nucleus, core; AcbS: Accumbens nucleus, shell; DLS: Dorsolateral striatum; DMS: Dorsomedial striatum; SNc: Substantia nigra, compacta; SNR: Substantia nigra, reticulata; Tu: Olfactory tubercle; VTA: ventral tegmental area. (B) Dark-field microphotographs from [³H]SCH23390-, [³H]Raclopride and [³H]Mazindol binding, and (C) in situ hybridization signal of D1, D2, DAT and TH mRNA on brain sections of naive C57/Bl6 male mice. For details on treatment, see Section Materials and Methods.

Figure 2

Spatiotemporal pattern of D1 and D2 binding in the dorsal striatum 1 week after the acquisition or consolidation of skill learning. Performance of the animals on the accelerating rotarod for the early (A) and late (B) experimental groups. Latency to fall off the rotarod throughout all training session is shown. (C) Ligand binding to D1 and D2 receptors in the dorsomedial (DMS) and dorsolateral (DLS) striatum. Data are presented as percentage (±SEM) of specific binding from the untreated control animals. * p < 0.05, *** p < 0.001 vs. control group. # p < 0.05 early vs. late group. (D) Ratio of D1/D2 receptors in DMS and DLS after the early and late training phase. * p < 0.05 early vs. late in DMS. For detailed statistics see text.