Striatal GluN2B involved in motor skill learning and stimulus-response learning

Abstract

Although the striatum has a well-documented role in procedural learning and memory, the underlying mechanisms remain poorly understood. GluN2B subunit is abundantly expressed in striatum, however, the function of striatal GluN2B subunit in striatum-related learning is also unclear. In the present study, using transgenic mice with forebrain-specific overexpression of the GluN2B subunit, we observed that up-regulation of GluN2B subunit expression results in enhanced dorsal striatum-related motor skill learning and stimulus-response (S-R) learning as well as cortico-dorsomedial striatal (cortico-DMS) long-term potentiation (LTP). Consistent with the above results, we also found that GluN2B transgenic mice exhibited a remarkable increase in N-methyl-d-aspartic acid receptor (NMDAR) mediated currents in the dorsomedial striatum. In addition, in order to further verify that striatal GluN2B is involved in the dorsal striatum-related cognitive function, lentivirus-mediated short hairpin RNA (shRNA) was used to silence the expression of GluN2B gene in the dorsomedial striatum. As a consequence of down-regulation of dorsomedial striatal GluN2B subunit expression, defective motor skill learning and S-R learning were observed in the GluN2B-shRNA mice. Furthermore, the impaired cortico-DMS LTP, as well as decreased NMDAR mediated currents in the dorsomedial striatum were also detected. Taken together, our findings demonstrate for the first time that striatal GluN2B subunit plays an important role in the dorsal striatum-related motor skill learning and S-R learning and provide further evidence that the cortico-DMS LTP underlies dorsal striatum-related motor skill learning and S-R learning.

Keywords: Dorsal striatum; GluN2B; LTP; Motor skill learning; NMDAR; S-R learning.