Striatopallidal adenosine A2A receptors in the nucleus accumbens confer motivational control of goal-directed behavior
Striatopallidal adenosine A2A receptors in the nucleus accumbens confer motivational control of goal-directed behavior
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伏隔核中的纹状体苍白球腺苷 A2A 受体赋予目标导向行为的动机控制
DOI：
10.1016/j.neuropharm.2020.108010
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发表时间：
2020
影响因子：
4.7
通讯作者：
Jiang-fan Chen
中科院分区：
文献类型：
--
作者：
Yan Li;Yang Ruan;Yan He;Qionghui Cai;Xinran Pan;Yu Zhang;Chengwei Liu;Zhilan Pu;Jingjing Yang;Mozi Chen;Linshan Huang;Jianhong Zhou;Jiang-fan Chen
学习动态环境中的奖励-价值和行动-结果偶然性的能力对灵活的适应行为至关重要，目标导向行为的有效药理控制的发展是改善目标导向行为缺陷的重要挑战，目标导向行为缺陷可能是精神疾病中看似不同症状的基础。腺苷a2a受体（A2AR）因其独特的神经调节特征而成为控制目标导向行为的新型神经调节靶点：整合多巴胺和谷氨酸信号的能力，各种认知过程的“制动”约束以及目标导向和习惯行为的平衡控制。然而，伏隔核（NAc）纹状体A2ARs在控制目标导向行为中的作用和回路机制仍有待确定。在这里，我们采用新开发的opto-A2AR和focal A2AR敲除策略来证明NAc A2AR在控制目标导向行为中的因果作用。此外，我们剖析了NAc A2ARs控制目标导向行为的多种不同行为机制：(i) NAc A2ARs优先控制目标导向行为，而牺牲习惯形成。（ii） NAc - A2ARs在不影响行动-结果偶然性的情况下，改变了动物对奖励价值的敏感性。（iii） A2AR拮抗剂KW6002通过激活动机促进工具性行为。NAc - a2ar促进了巴甫洛夫激励价值向工具行为的转移。(v) NAc- A2ARs控制目标导向行为可能不是通过NAc- vp途径。这些关于NAc A2AR控制目标导向行为的行为和回路机制的见解，促进了A2AR拮抗剂在逆转与多种神经精神疾病相关的目标导向决策缺陷方面的转化潜力。
The ability to learn the reward-value and action-outcome contingencies in dynamic environment is critical for flexible adaptive behavior and development of effective pharmacological control of goal-directed behaviors represents an important challenge for improving the deficits in goal-directed behavior which may underlie seemingly disparate symptoms across psychiatric disorders. Adenosine A2Areceptor (A2AR) is emerging as a novel neuromodulatory target for controlling goal-directed behavior for its unique neuromodulatory features: the ability to integrate dopamine and glutamate signaling, the “brake” constraint of various cognitive processes and the balanced control of goal-directed and habit actions. However, the contribution and circuit mechanisms of the striatopallidal A2ARs in nucleus accumbens (NAc) to control of goal-directed behavior remain to be determined. Here, we employed newly developed opto-A2AR and the focal A2AR knockdown strategies to demonstrate the causal role of NAc A2AR in control of goal-directed behavior. Furthermore, we dissected out multiple distinct behavioral mechanisms underlying which NAc A2ARs control goal-directed behavior: (i) NAc A2ARs preferentially control goal-directed behavior at the expense of habit formation. (ii) NAc A2ARs modify the animals’ sensitivity to the value of the reward without affecting the action-outcome contingency. (iii) A2AR antagonist KW6002 promotes instrumental actions by invigorating motivation. (iv) NAc A2ARs facilitate Pavlovian incentive value transferring to instrumental action. (v) NAc A2ARs control goal-directed behavior probably not through NAc-VP pathway. These insights into the behavioral and circuit mechanisms for NAc A2AR control of goal-directed behavior facilitate translational potential for A2AR antagonists in reversal of deficits in goal-directed decision-making associated with multiple neuropsychiatric disorders.