PDF(Pubmed)
Abstract：
Reversal learning measures the ability to form flexible associations between choice outcomes with stimuli and actions that precede them. This type of learning is thought to rely on several cortical and subcortical areas, including the highly interconnected orbitofrontal cortex (OFC) and basolateral amygdala (BLA), and is often impaired in various neuropsychiatric and substance use disorders. However, the unique contributions of these regions to stimulus- and action-based reversal learning have not been systematically compared using a chemogenetic approach particularly before and after the first reversal that introduces new uncertainty. Here, we examined the roles of ventrolateral OFC (vlOFC) and BLA during reversal learning. Male and female rats were prepared with inhibitory designer receptors exclusively activated by designer drugs targeting projection neurons in these regions and tested on a series of deterministic and probabilistic reversals during which they learned about stimulus identity or side (left or right) associated with different reward probabilities. Using a counterbalanced within-subject design, we inhibited these regions prior to reversal sessions. We assessed initial and pre-/post-reversal changes in performance to measure learning and adjustments to reversals, respectively. We found that inhibition of the ventrolateral orbitofrontal cortex (vlOFC), but not BLA, eliminated adjustments to stimulus-based reversals. Inhibition of BLA, but not vlOFC, selectively impaired action-based probabilistic reversal learning, leaving deterministic reversal learning intact. vlOFC exhibited a sex-dependent role in early adjustment to action-based reversals, but not in overall learning. These results reveal dissociable roles for BLA and vlOFC in flexible learning and highlight a more crucial role for BLA in learning meaningful changes in the reward environment.
摘要：
逆向学习衡量在选择结果与刺激和之前的动作之间形成灵活关联的能力。这种类型的学习被认为依赖于几个皮质和皮质下区域，包括高度互联的眶额皮质（OFC）和基底外侧杏仁核（BLA），并且经常在各种神经精神和物质使用障碍中受损。然而,尚未使用化学遗传学方法系统地比较这些区域对基于刺激和作用的逆转学习的独特贡献，特别是在引入新不确定性的第一次逆转之前和之后。这里,我们研究了腹侧OFC（vlOFC）和BLA在逆转学习中的作用。雄性和雌性大鼠准备有针对这些区域中的投射神经元的抑制性DREADD，并在一系列确定性和概率逆转中进行测试，在此期间，他们了解了与不同奖励概率相关的刺激身份或侧面（左侧或右侧）。使用平衡的主题内设计，我们在逆转会议之前抑制了这些区域。我们评估了最初和逆转前的绩效变化，以衡量学习和对逆转的调整，分别。我们发现vlOFC的抑制作用,但不是BLA,取消了对基于刺激的逆转的调整。抑制BLA,但不是VLOFC，选择性受损的基于动作的概率反转学习，保持确定性反转学习不变。vlOFC在早期适应基于行动的逆转中表现出性别依赖性作用，但不是整体学习。这些结果揭示了BLA和vlOFC在灵活学习中的可分离作用，并强调了BLA在学习奖励环境中有意义的变化中的更重要作用。重要性陈述僵化学习是几种神经精神疾病的特征。我们研究了腹外侧眶额皮质（vlOFC）和基底外侧杏仁核（BLA）如何参与增强不确定性下的刺激或动作的学习。在男性和女性中对这些区域进行化学遗传抑制后，我们测量了学习和对确定性和概率逆转的调整。对于行动学习，BLA,但不是VLOFC，是概率反转学习所需要的。然而,BLA不是初始概率学习或保留所必需的，表明对学习意外变化的关键作用。对于刺激学习，vlOFC,但不是BLA,需要调整逆转，尤其是女性。这些发现提供了在不同形式的不确定性下学习的互补皮质-杏仁核底物的见解。
