| First Author | Iino Y | Year | 2020 |
| Journal | Nature | Volume | 579 |
| Issue | 7800 | Pages | 555-560 |
| PubMed ID | 32214250 | Mgi Jnum | J:293012 |
| Mgi Id | MGI:6445650 | Doi | 10.1038/s41586-020-2115-1 |
| Citation | Iino Y, et al. (2020) Dopamine D2 receptors in discrimination learning and spine enlargement. Nature 579(7800):555-560 |
| abstractText | Dopamine D2 receptors (D2Rs) are densely expressed in the striatum and have been linked to neuropsychiatric disorders such as schizophrenia(1,2). High-affinity binding of dopamine suggests that D2Rs detect transient reductions in dopamine concentration (the dopamine dip) during punishment learning(3-5). However, the nature and cellular basis of D2R-dependent behaviour are unclear. Here we show that tone reward conditioning induces marked stimulus generalization in a manner that depends on dopamine D1 receptors (D1Rs) in the nucleus accumbens (NAc) of mice, and that discrimination learning refines the conditioning using a dopamine dip. In NAc slices, a narrow dopamine dip (as short as 0.4 s) was detected by D2Rs to disinhibit adenosine A2A receptor (A2AR)-mediated enlargement of dendritic spines in D2R-expressing spiny projection neurons (D2-SPNs). Plasticity-related signalling by Ca(2+)/calmodulin-dependent protein kinase II and A2ARs in the NAc was required for discrimination learning. By contrast, extinction learning did not involve dopamine dips or D2-SPNs. Treatment with methamphetamine, which dysregulates dopamine signalling, impaired discrimination learning and spine enlargement, and these impairments were reversed by a D2R antagonist. Our data show that D2Rs refine the generalized reward learning mediated by D1Rs. |
