PMID- 29505785 OWN - NLM STAT- MEDLINE DCOM- 20190204 LR - 20190215 IS - 1873-7064 (Electronic) IS - 0028-3908 (Linking) VI - 135 DP - 2018 Jun TI - Striatal GluN2B involved in motor skill learning and stimulus-response learning. PG - 73-85 LID - S0028-3908(18)30103-5 [pii] LID - 10.1016/j.neuropharm.2018.03.002 [doi] AB - 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. CI - Copyright (c) 2018 Elsevier Ltd. All rights reserved. FAU - Duan, Yanhong AU - Duan Y AD - Key Laboratory of Brain Functional Genomics, Ministry of Education, Shanghai Key Laboratory of Brain Functional Genomics, School of Life Sciences, East China Normal University, Shanghai, China. FAU - Wang, Qi AU - Wang Q AD - Key Laboratory of Brain Functional Genomics, Ministry of Education, Shanghai Key Laboratory of Brain Functional Genomics, School of Life Sciences, East China Normal University, Shanghai, China. FAU - Zeng, Qingwen AU - Zeng Q AD - Key Laboratory of Brain Functional Genomics, Ministry of Education, Shanghai Key Laboratory of Brain Functional Genomics, School of Life Sciences, East China Normal University, Shanghai, China. FAU - Wang, Jiayue AU - Wang J AD - Key Laboratory of Brain Functional Genomics, Ministry of Education, Shanghai Key Laboratory of Brain Functional Genomics, School of Life Sciences, East China Normal University, Shanghai, China. FAU - Chen, Zhenzhen AU - Chen Z AD - Key Laboratory of Brain Functional Genomics, Ministry of Education, Shanghai Key Laboratory of Brain Functional Genomics, School of Life Sciences, East China Normal University, Shanghai, China. FAU - Xu, Meichen AU - Xu M AD - Key Laboratory of Brain Functional Genomics, Ministry of Education, Shanghai Key Laboratory of Brain Functional Genomics, School of Life Sciences, East China Normal University, Shanghai, China. FAU - Duan, Yale AU - Duan Y AD - Key Laboratory of Brain Functional Genomics, Ministry of Education, Shanghai Key Laboratory of Brain Functional Genomics, School of Life Sciences, East China Normal University, Shanghai, China. FAU - Zhao, Zheng AU - Zhao Z AD - Key Laboratory of Brain Functional Genomics, Ministry of Education, Shanghai Key Laboratory of Brain Functional Genomics, School of Life Sciences, East China Normal University, Shanghai, China. FAU - Xue, Qingsheng AU - Xue Q AD - Department of Anesthesiology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China. Electronic address: xqs11260@rjh.com.cn. FAU - Cao, Xiaohua AU - Cao X AD - Key Laboratory of Brain Functional Genomics, Ministry of Education, Shanghai Key Laboratory of Brain Functional Genomics, School of Life Sciences, East China Normal University, Shanghai, China. Electronic address: xhcao@brain.ecnu.edu.cn. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20180302 PL - England TA - Neuropharmacology JT - Neuropharmacology JID - 0236217 RN - 0 (NR2B NMDA receptor) RN - 0 (RNA, Small Interfering) RN - 0 (Receptors, N-Methyl-D-Aspartate) SB - IM MH - Animals MH - Corpus Striatum/physiology MH - Down-Regulation MH - Learning/*physiology MH - Long-Term Potentiation/physiology MH - Male MH - Mice MH - Mice, Transgenic MH - Motor Skills/*physiology MH - Neostriatum/metabolism MH - RNA, Small Interfering/pharmacology MH - Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors/biosynthesis/genetics/*physiology MH - Up-Regulation OTO - NOTNLM OT - Dorsal striatum OT - GluN2B OT - LTP OT - Motor skill learning OT - NMDAR OT - S-R learning EDAT- 2018/03/06 06:00 MHDA- 2019/02/05 06:00 CRDT- 2018/03/06 06:00 PHST- 2017/11/03 00:00 [received] PHST- 2018/02/27 00:00 [revised] PHST- 2018/03/01 00:00 [accepted] PHST- 2018/03/06 06:00 [pubmed] PHST- 2019/02/05 06:00 [medline] PHST- 2018/03/06 06:00 [entrez] AID - S0028-3908(18)30103-5 [pii] AID - 10.1016/j.neuropharm.2018.03.002 [doi] PST - ppublish SO - Neuropharmacology. 2018 Jun;135:73-85. doi: 10.1016/j.neuropharm.2018.03.002. Epub 2018 Mar 2.