δ-Opioid and Dopaminergic Processes in Accumbens Shell Modulate the Cholinergic Control of Predictive Learning and Choice
δ-Opioid and Dopaminergic Processes in Accumbens Shell Modulate the Cholinergic Control of Predictive Learning and Choice
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DOI：
10.1523/jneurosci.4592-13.2014
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发表时间：
2014-01-22
影响因子：
5.3
通讯作者：
Balleine, Bernard W.
中科院分区：
文献类型：
--
作者：
Laurent, Vincent;Bertran-Gonzalez, Jesus;Balleine, Bernard W.
决策取决于从环境中提取预测信息以指导未来行动的能力。结果特异性巴甫洛夫工具性迁移（PIT）提供了一个动物模型，在这个模型中，预测特定结果的刺激会使选择偏向于获得该结果的行为。最近的证据表明，δ阿片受体（DORs）的细胞适应的胆碱能中间神经元（CINs）在核壳（NAc-S）是必要的PIT。在这里，我们发现在CIN中DORs的调节严重影响NAc-S中表达D-1受体（D1 R）的投射神经元以促进PIT。首先，我们使用drd 2-eGFP小鼠评估了PIT诱导的多巴胺D-1和D-2受体表达神经元信号传导过程的变化，发现PIT相关信号传导仅限于非D2 R-eGFP表达神经元，表明D1 R神经元的主要参与。接下来，我们证实了D1 R拮抗剂SCH-23390的作用：D1 R拮抗剂SCH-23390，而不是D2 R拮抗剂雷氯必利，注入大鼠的NAc-S消除PIT，这种作用依赖于DOR活性。此外，向NAc-S不对称输注SCH-23390和DOR拮抗剂纳曲吲哚也可消除PIT。发现DOR激动剂使PIT试验后立即制备的脑切片中的CIN的放电反应敏感。我们通过选择性地阻断NAc-S中的毒蕈碱M4受体来证实阿片样乙酰胆碱能对D1 R神经元的影响，NAc-S中的毒蕈碱M4受体严格调节D1 R的活性，这是一种挽救纳曲吲哚诱导的PIT缺陷的治疗。我们描述了一个NAc-S功能模型，其中DORs调节CINs以影响D1 R神经元和刺激引导的目标导向行为之间的选择。
Decision-making depends on the ability to extract predictive information from the environment to guide future actions. Outcome-specific Pavlovian-instrumental transfer (PIT) provides an animal model of this process in which a stimulus predicting a particular outcome biases choice toward actions earning that outcome. Recent evidence suggests that cellular adaptations of delta-opioid receptors (DORs) on cholinergic interneurons (CINs) in the nucleus accumbens shell (NAc-S) are necessary for PIT. Here we found that modulation of DORs in CINs critically influences D-1-receptor(D1R)-expressing projection neurons in the NAc-S to promote PIT. First, we assessed PIT-induced changes in signaling processes in dopamine D-1- and D-2-receptor-expressing neurons using drd2-eGFP mice, and found that PIT-related signaling was restricted to non-D2R-eGFP-expressing neurons, suggesting major involvement of D1R-neurons. Next we confirmed the role of D1Rs pharmacologically: the D1R antagonist SCH-23390, but not the D2R antagonist raclopride, infused into the NAc-Sabolished PIT in rats, an effect that depended on DOR activity. Moreover, asymmetrical infusion of SCH-23390 and the DOR antagonist naltrindole into the NAc-S also abolished PIT. DOR agonists were found to sensitize the firing responses of CINs in brain slices prepared immediately after the PIT test. We confirmed the opioid-acetylcholinergic influence over D1R-neurons by selectively blocking muscarinic M4 receptors in the NAc-S, which tightly regulate the activity of D1Rs, a treatment that rescued the deficit in PIT induced by naltrindole. We describe a model of NAc-S function in which DORs modulate CINs to influence both D1R-neurons and stimulus-guided choice between goal-directed actions.