Acquisition and performance of goal-directed instrumental actions depends on ERK signaling in distinct regions of dorsal striatum in rats.
Acquisition and performance of goal-directed instrumental actions depends on ERK signaling in distinct regions of dorsal striatum in rats.
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目标导向工具性动作的获得和执行取决于大鼠背侧纹状体不同区域的 ERK 信号传导。
DOI：
10.1523/jneurosci.1778-09.2010
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发表时间：
2010-02-24
期刊：
影响因子：
--
通讯作者：
Balleine BW
中科院分区：
文献类型：
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作者：
Shiflett MW;Brown RA;Balleine BW
以目标为导向的行动的执行依赖于动物对其行动所产生的结果或后果的先验知识。此外，将环境刺激与动作联系起来的感觉运动学习过程通过选择进一步评估的动作来影响仪器性能。啮齿动物的这些不同的决策过程取决于背侧纹状体的不同子区域。背内侧纹状体后部（pDMS）需要编码动作及其结果或后果，而背外侧纹状体（DLS）则根据感觉运动学习介导动作选择。然而，这些大脑区域内支持学习和执行目标导向行为的分子机制尚不清楚。在这里，我们表明，背侧纹状体中细胞外信号调节激酶（ERK）的激活对于啮齿类动物的工具性目标导向行为的学习和表现具有关键作用。我们观察到在最近获得的工具性目标导向动作的采集和执行过程中，pDMS 和 DLS 中 p42 ERK (ERK2) 的激活有所增加。此外，pDMS 中 ERK 激活的破坏阻止了行动-结果关联的获得，以及由先前获得的关联引导的目标导向行动的执行，而 DLS 中 ERK 激活的破坏破坏了工具性表现，同时使工具性行动-结果学习完好无损。这些结果提供了证据，证明背侧纹状体中 ERK 信号传导在工具学习获取过程中发挥着关键的、区域特异性的作用，并表明这些纹状体亚区域内对 ERK 信号传导敏感的过程相互作用，以控制初始获取后的工具表现。
The performance of goal-directed actions relies on an animal’s prior knowledge of the outcomes or consequences that result from its actions. Additionally, a sensorimotor learning process linking environmental stimuli with actions influences instrumental performance by selecting actions for further evaluation. These distinct decision-making processes in rodents depend on separate sub-regions of the dorsal striatum. Whereas the posterior dorsomedial striatum (pDMS) is required for the encoding of actions with their outcomes or consequences, the dorsolateral striatum (DLS) mediates action-selection based on sensorimotor learning. However, the molecular mechanisms within these brain regions that support learning and performance of goal-directed behavior are not known. Here we show that activation of extracellular signal-regulated kinase (ERK) in the dorsal striatum has a critical role in learning and performance of instrumental goal-directed behavior in rodents. We observed an increase in p42 ERK (ERK2) activation in both the pDMS and DLS during both the acquisition and performance of recently acquired instrumental goal-directed actions. Furthermore, disruption of ERK activation in the pDMS prevented both the acquisition of action-outcome associations, as well as the performance of goal-directed actions guided by previously acquired associations, whereas disruption of ERK activation in the DLS disrupted instrumental performance while leaving instrumental action-outcome learning intact. These results provide evidence of a critical, region-specific role for ERK signaling in the dorsal striatum during the acquisition of instrumental learning and suggest that processes sensitive to ERK signaling within these striatal subregions interact to control instrumental performance after initial acquisition.