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Amphetamine disrupts haemodynamic correlates of prediction errors in nucleus accumbens and orbitofrontal cortex.
Neuropsychopharmacology ( IF 7.6 ) Pub Date : 2019-11-08 , DOI: 10.1038/s41386-019-0564-8
Emilie Werlen 1 , Soon-Lim Shin 1 , Francois Gastambide 2 , Jennifer Francois 2 , Mark D Tricklebank 3 , Hugh M Marston 2 , John R Huxter 2 , Gary Gilmour 2 , Mark E Walton 1, 4
Affiliation  

In an uncertain world, the ability to predict and update the relationships between environmental cues and outcomes is a fundamental element of adaptive behaviour. This type of learning is typically thought to depend on prediction error, the difference between expected and experienced events and in the reward domain that has been closely linked to mesolimbic dopamine. There is also increasing behavioural and neuroimaging evidence that disruption to this process may be a cross-diagnostic feature of several neuropsychiatric and neurological disorders in which dopamine is dysregulated. However, the precise relationship between haemodynamic measures, dopamine and reward-guided learning remains unclear. To help address this issue, we used a translational technique, oxygen amperometry, to record haemodynamic signals in the nucleus accumbens (NAc) and orbitofrontal cortex (OFC), while freely moving rats performed a probabilistic Pavlovian learning task. Using a model-based analysis approach to account for individual variations in learning, we found that the oxygen signal in the NAc correlated with a reward prediction error, whereas in the OFC it correlated with an unsigned prediction error or salience signal. Furthermore, an acute dose of amphetamine, creating a hyperdopaminergic state, disrupted rats’ ability to discriminate between cues associated with either a high or a low probability of reward and concomitantly corrupted prediction error signalling. These results demonstrate parallel but distinct prediction error signals in NAc and OFC during learning, both of which are affected by psychostimulant administration. Furthermore, they establish the viability of tracking and manipulating haemodynamic signatures of reward-guided learning observed in human fMRI studies by using a proxy signal for BOLD in a freely behaving rodent.



中文翻译:

苯丙胺会破坏伏伏核和眶额皮层预测误差的血流动力学相关性。

在不确定的世界中,预测和更新环境提示与结果之间关系的能力是适应性行为的基本要素。通常认为这种学习取决于预测误差,预期事件和经历事件之间的差异以及与中脑边缘多巴胺密切相关的奖励领域。越来越多的行为和神经影像学证据表明,对该过程的破坏可能是多巴胺失调的几种神经精神疾病和神经疾病的交叉诊断特征。然而,血流动力学测量,多巴胺与奖励指导学习之间的确切关系仍不清楚。为了帮助解决此问题,我们使用了一种翻译技术,氧气安培计,记录伏隔核(NAc)和眶额皮质(OFC)中的血流动力学信号,而自由移动的大鼠则执行概率性的巴甫洛夫式学习任务。使用基于模型的分析方法来说明学习中的个体差异,我们发现NAc中的氧信号与奖励预测误差相关,而在OFC中,氧信号与无符号预测误差或显着信号相关。此外,急性剂量的苯丙胺会产生高多巴胺能状态,破坏大鼠区分与高或低奖励率相关的线索的能力,并同时破坏预测误差信号。这些结果证明了学习期间NAc和OFC中的平行但截然不同的预测误差信号,这两者均受精神刺激药管理的影响。

更新日期:2019-11-08
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