Striatal GluN2B involved in motor skill learning and stimulus-response learning
Striatal GluN2B involved in motor skill learning and stimulus-response learning
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纹状体 GluN2B 参与运动技能学习和刺激反应学习
DOI：
10.1016/j.neuropharm.2018.03.002
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发表时间：
2018-06-01
影响因子：
4.7
通讯作者：
Cao, Xiaohua
中科院分区：
文献类型：
--
作者：
Duan, Yanhong;Wang, Qi;Cao, Xiaohua
虽然纹状体在程序性学习和记忆中的作用有充分的证据，但其潜在机制仍然知之甚少。GluN 2B亚基在纹状体中大量表达，但其在纹状体相关学习中的功能尚不清楚。在本研究中，使用前脑特异性过表达GluN 2B亚基的转基因小鼠，我们观察到，上调GluN 2B亚基表达的结果在增强背侧纹状体相关的运动技能学习和刺激反应（S-R）学习以及皮质-背内侧纹状体（皮质-DMS）的长时程增强（LTP）。与上述结果一致，我们还发现，GluN 2B转基因小鼠表现出显着增加的N-甲基-D-天冬氨酸受体（NMDAR）介导的电流在背内侧纹状体。此外，为了进一步验证纹状体GluN 2B是否参与背侧纹状体相关的认知功能，我们采用慢病毒介导的短发夹RNA（shRNA）沉默背内侧纹状体GluN 2B基因的表达。由于背内侧纹状体GluN 2B亚基表达下调，在GluN 2B-shRNA小鼠中观察到运动技能学习和S-R学习缺陷。此外，还检测到背内侧纹状体皮质-DMS LTP受损以及NMDAR介导的电流减少。总而言之，我们的研究结果首次证明了纹状体GluN 2B亚基在背侧纹相关运动技能学习和S-R学习中发挥重要作用，并进一步证明皮质-DMS LTP是背侧纹相关运动技能学习和S-R学习的基础。(C)2018爱思唯尔有限公司版权所有
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. (C) 2018 Elsevier Ltd. All rights reserved.