Dopamine D2 receptor signaling on iMSNs is required for initiation and vigor of learned actions.
Dopamine D2 receptor signaling on iMSNs is required for initiation and vigor of learned actions.
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DOI：
10.1038/s41386-020-00799-1
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发表时间：
2020-11
期刊：
影响因子：
--
通讯作者：
Lovinger DM
中科院分区：
文献类型：
--
作者：
Augustin SM;Loewinger GC;O'Neal TJ;Kravitz AV;Lovinger DM
纹状体多巴胺D2受体(D2Rs)对运动输出很重要。间接通路投射介质棘神经元(IMSN)中D2Rs的选择性缺失以任务特异性的方式损害运动活动。然而，D2Rs在奖赏寻求和接受中启动运动动作中的作用还不完全清楚，关于受体在不同任务要求和不同结果类型下如何发挥作用的信息也很少。IMSN-D2Rs调节神经元活动和突触传递，对可能在动作学习和执行中发挥不同作用的电路功能施加控制。在工具性条件反射任务中，选择性删除iMSN上的D2R会导致较慢的动作启动和反应速度，但只有当性能需求增加时才会如此。IMSN-Drd2KO小鼠在T迷宫程序性学习任务中开始游泳的速度也较慢，但在认知功能和行为灵活性方面没有受到损害。相比之下，在巴甫洛夫辨别学习任务中，IMSN-Drd2KO小鼠表现出正常的奖赏反应获得和消退。IMSN-Drd2KO小鼠在旋转棒技能学习的所有阶段都表现出成绩缺陷。这些发现表明，通过IMSN-D2Rs的多巴胺调节影响了自我启动动作的能力，以及执行这些反应的意愿和/或活力。然而，这些受体似乎对简单的联想学习或刺激驱动的反应几乎没有影响。正常D2R角色的丧失可能导致功能障碍，其中多巴胺信号受损导致运动减退或特定自愿行为的启动受损。
Striatal dopamine D2 receptors (D2Rs) are important for motor output. Selective deletion of D2Rs from indirect pathway-projecting medium spiny neurons (iMSNs) impairs locomotor activities in a task-specific manner. However, the role of D2Rs in the initiation of motor actions in reward seeking and taking is not fully understood, and there is little information about how receptors contribute under different task demands and with different outcome types. The iMSN-D2Rs modulate neuronal activity and synaptic transmission, exerting control on circuit functions that may play distinct roles in action learning and performance. Selective deletion of D2Rs on iMSNs resulted in slower action initiation and response rate in an instrumental conditioning task, but only when performance demand was increased. The iMSN-Drd2KO mice were also slower to initiate swimming in a T-maze procedural learning task but were unimpaired in cognitive function and behavioral flexibility. In contrast, in a Pavlovian discrimination learning task, iMSN-Drd2KO mice exhibited normal acquisition and extinction of rewarded responding. The iMSN-Drd2KO mice showed performance deficits at all phases of rotarod skill learning. These findings reveal that dopamine modulation through iMSN-D2Rs influences the ability to self-initiate actions, as well as the willingness and/or vigor with which these responses are performed. However, these receptors seem to have little influence on simple associative learning or on stimulus-driven responding. The loss of normal D2R roles may contribute to disorders in which impaired dopamine signaling leads to hypokinesia or impaired initiation of specific voluntary actions.
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