Striatal cholinergic interneurons (CINs) are key to regulating behavioral flexibility, involving both extinguishing learned actions and adopting new ones. However, the mechanisms driving these processes remain elusive. In this study, we initially demonstrate that chronic alcohol consumption disrupts the burst-pause dynamics of CINs and impairs behavioral flexibility. We next aimed to elucidate the mechanisms by which CIN dynamics control behavioral flexibility. We found that extinction learning enhances acetylcholine (ACh) release and that mimicking this enhancement through optogenetic induction of CIN burst firing accelerates the extinction process. In addition, we demonstrate that disrupting CIN pauses via continuous optogenetic stimulation reversibly impairs the updating of goal-directed behaviors. Overall, we demonstrate that CIN burst firing, which increases ACh release, promotes extinction learning, aiding the extinguishment of learned behaviors. Conversely, CIN firing pauses, which lead to ACh dips, are crucial for reversal learning, facilitating the adaptation of new actions. These findings shed light on how CIN dynamics regulate behavioral flexibility.

中文翻译：

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纹状体胆碱能中间神经元的动态反应控制行为灵活性


纹状体胆碱能中间神经元 （CIN） 是调节行为灵活性的关键，包括消除习得的动作和采用新的动作。然而，驱动这些过程的机制仍然难以捉摸。在这项研究中，我们初步证明长期饮酒会破坏 CIN 的突发暂停动力学并损害行为灵活性。接下来，我们旨在阐明 CIN 动力学控制行为灵活性的机制。我们发现消光学习增强了乙酰胆碱 （ACh） 的释放，并且通过 CIN 爆发放电的光遗传学诱导来模拟这种增强会加速消光过程。此外，我们证明通过连续光遗传学刺激破坏 CIN 暂停会可逆地损害目标导向行为的更新。总体而言，我们证明 CIN 突发放电可增加 ACh 释放，促进消退学习，有助于消灭习得行为。相反，导致 ACh 下降的 CIN 触发暂停对于逆向学习至关重要，有助于适应新动作。这些发现揭示了 CIN 动力学如何调节行为灵活性。