The role of prefrontal dopamine D1 receptors in the neural mechanisms of associative learning.
The role of prefrontal dopamine D1 receptors in the neural mechanisms of associative learning.
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DOI：
10.1016/j.neuron.2012.04.018
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发表时间：
2012-06-07
期刊：
影响因子：
16.2
通讯作者：
Miller EK
中科院分区：
文献类型：
--
作者：
Puig MV;Miller EK
多巴胺被认为在学习中起着重要作用。然而，虽然前额叶皮层（PFC）中的多巴胺D1受体（D1R）已被证明可以调节与工作记忆相关的神经活动，但它们在学习的细胞基础中的作用尚不清楚。当猴子学习视觉关联时，我们在外侧PFC中注射D1R拮抗剂SCH 23390时记录了多个电极的活动。阻断D1Rs会损害新联想的学习，降低认知灵活性，但不会影响已经熟悉的联想。这表明前额叶D1R在学习新事物方面的作用比熟悉的联想更大。有一个相应的更大的减少，神经选择性和增加α和β振荡的局部场电位的新比熟悉的协会。我们的研究结果表明，在衰老和精神疾病中观察到的D1Rs的弱刺激可能会通过降低神经选择性和加剧与注意力不集中和认知缺陷相关的神经振荡来损害学习和PFC功能。
Dopamine is thought to play a major role in learning. However, while dopamine D1 receptors (D1Rs) in the prefrontal cortex (PFC) have been shown to modulate working memory-related neural activity, their role in the cellular basis of learning is unknown. We recorded activity from multiple electrodes while injecting the D1R antagonist SCH23390 in the lateral PFC as monkeys learned visuomotor associations. Blocking D1Rs impaired learning of novel associations and decreased cognitive flexibility, but spared performance of already familiar associations. This suggests a greater role for prefrontal D1Rs in learning new, than performing familiar, associations. There was a corresponding greater decrease in neural selectivity and increase in alpha and beta oscillations in local field potentials for novel than familiar associations. Our results suggest that weak stimulation of D1Rs observed in aging and psychiatric disorders may impair learning and PFC function by reducing neural selectivity and exacerbating neural oscillations associated with inattention and cognitive deficits.
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影响因子：
10.6
作者：
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通讯作者：
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DOI：
10.1073/pnas.0609440103
发表时间：
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