Spatially restricted inhibition of cholinergic interneurons in the dorsolateral striatum encourages behavioral exploration,European Journal of Neuroscience

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Spatially restricted inhibition of cholinergic interneurons in the dorsolateral striatum encourages behavioral exploration
European Journal of Neuroscience ( IF 2.7 ) Pub Date : 2021-01-19 , DOI: 10.1111/ejn.15117
Kenneth A Amaya ₁ , Kyle S Smith ₁

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When pursuing desirable outcomes, one must make the decision between exploring possible actions to obtain those outcomes and exploiting known strategies to maximize efficiency. The dorsolateral striatum (DLS) has been extensively studied with respect to how actions can develop into habits and has also been implicated as an area involved in governing exploitative behavior. Surprisingly, prior work has shown that DLS cholinergic interneurons (ChIs) are not involved in the canonical habit formation function ascribed to the DLS but are instead modulators of behavioral flexibility after initial learning. To further probe this, we evaluated the role of DLS ChIs in behavioral exploration during a brief instrumental training experiment. Through designer receptors exclusively activated by designer drugs (DREADDs) in ChAT‐Cre rats, ChIs in the DLS were inhibited during specific phases of the experiment: instrumental training, free‐reward delivery, at both times, or never. Without ChI activity during instrumental training, animals biased their responding toward an “optimal” strategy while continuing to work efficiently. This effect was observed again when contingencies were removed as animals with ChIs offline during that phase, regardless of ChI inhibition previously, decreased responding more than animals with ChIs intact. These findings build upon a growing body of literature implicating ChIs in the striatum as gate‐keepers of behavioral flexibility and exploration.

中文翻译：

对背外侧纹状体胆碱能中间神经元的空间限制抑制促进了行为探索

在追求理想结果时，必须在探索获得这些结果的可能行动和利用已知策略以最大限度地提高效率之间做出决定。背外侧纹状体 (DLS) 已被广泛研究，以了解行为如何发展成习惯，并且还被认为是控制剥削行为的一个领域。令人惊讶的是，先前的工作表明 DLS 胆碱能中间神经元 (ChIs) 不参与归因于 DLS 的规范习惯形成功能，而是在初始学习后成为行为灵活性的调节剂。为了进一步探讨这一点，我们在简短的仪器训练实验中评估了 DLS Chis 在行为探索中的作用。通过在 ChAT-Cre 大鼠中由设计药物 (DREADDs) 专门激活的设计受体，DLS 中的 ChIs 在实验的特定阶段受到抑制：器乐训练、免费奖励交付，无论是两次，还是从不。在器乐训练期间如果没有 ChI 活动，动物会在继续有效工作的同时将其反应偏向“最佳”策略。当意外事件被移除时，再次观察到这种效应，因为在该阶段具有 Chis 离线的动物，无论之前的 ChI 抑制如何，比具有完整 Chis 的动物的反应减少更多。这些发现建立在越来越多的文献基础上，这些文献表明纹状体中的 Chis 是行为灵活性和探索的守门人。动物在继续有效工作的同时，将它们的反应偏向于“最佳”策略。当意外事件被移除时，再次观察到这种效应，因为在该阶段具有 Chis 离线的动物，无论之前的 ChI 抑制如何，比具有完整 Chis 的动物的反应减少更多。这些发现建立在越来越多的文献基础上，这些文献表明纹状体中的 Chis 是行为灵活性和探索的守门人。动物在继续有效工作的同时，将它们的反应偏向于“最佳”策略。当意外事件被移除时，再次观察到这种效应，因为在该阶段具有 Chis 离线的动物，无论之前的 ChI 抑制如何，比具有完整 Chis 的动物的反应减少更多。这些发现建立在越来越多的文献基础上，这些文献表明纹状体中的 Chis 是行为灵活性和探索的守门人。

更新日期：2021-01-19

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