Johnson Alexander W, Crombag Hans S, Takamiya Kogo, Baraban Jay M, Holland Peter C, Huganir Richard L, Reti Irving M
Neurogenetics and Behavior Center, Johns Hopkins University, Baltimore, Maryland 21218, USA.
J Neurosci. 2007 Dec 5;27(49):13430-5. doi: 10.1523/JNEUROSCI.4320-07.2007.
Neuronal activity regulated pentraxin (Narp) is a secreted neuronal product which clusters AMPA receptors and regulates excitatory synaptogenesis. Although Narp is selectively enriched in brain, its role in behavior is not known. As Narp is expressed prominently in limbic regions, we examined whether Narp deletion affects performance on tasks used to assess motivational consequences of food-rewarded learning. Narp knock-out (KO) mice were unimpaired in learning simple pavlovian discriminations, instrumental lever pressing, and in acquisition of at least two aspects of pavlovian incentive learning, conditioned reinforcement and pavlovian-instrumental transfer. In contrast, Narp deletion resulted in a substantial deficit in the ability to use specific outcome expectancies to modulate instrumental performance in a devaluation task. In this task, mice were trained to respond on two levers for two different rewards. After training, mice were prefed with one of the two rewards, devaluing it. Responding on both levers was then assessed in extinction. Whereas control mice showed a significant preference in responding on the lever associated with the nondevalued reward, Narp KO mice responded equally on both levers, failing to suppress responding on the lever associated with the devalued reward. Both groups consumed more of the nondevalued reward in a subsequent choice test, indicating Narp KO mice could distinguish between the rewards themselves. These data suggest Narp has a selective role in processing sensory-specific information necessary for appropriate devaluation performance, but not in general motivational effects of reward-predictive cues on performance.
神经元活动调节五聚体蛋白（Narp）是一种分泌性神经元产物，它能使AMPA受体聚集并调节兴奋性突触的形成。尽管Narp在大脑中选择性富集，但其在行为中的作用尚不清楚。由于Narp在边缘区域显著表达，我们研究了Narp缺失是否会影响用于评估食物奖励学习的动机后果的任务表现。Narp基因敲除（KO）小鼠在学习简单的巴甫洛夫辨别任务、操作性杠杆按压以及获得巴甫洛夫奖励学习的至少两个方面（条件强化和巴甫洛夫-操作性转移）时未受损。相比之下，Narp缺失导致在贬值任务中利用特定结果预期来调节操作性表现的能力出现显著缺陷。在这个任务中，小鼠被训练在两个杠杆上做出反应以获得两种不同的奖励。训练后，给小鼠预先喂食两种奖励中的一种，使其对该奖励产生贬值。然后在消退阶段评估对两个杠杆的反应。对照小鼠在与未贬值奖励相关的杠杆上的反应表现出显著偏好，而Narp KO小鼠在两个杠杆上的反应相同，未能抑制在与贬值奖励相关的杠杆上的反应。在随后的选择测试中，两组小鼠都更多地消耗了未贬值的奖励，这表明Narp KO小鼠能够区分奖励本身。这些数据表明，Narp在处理适当贬值表现所需的特定感觉信息方面具有选择性作用，但在奖励预测线索对表现的一般动机影响方面并非如此。
