Department of Psychological & Brain Sciences, Krieger School of Arts & Sciences, Johns Hopkins University, Baltimore, MD, 21218, USA.
Department of Molecular and Cell Biology, University of California Berkeley, Berkeley, CA, 94720, USA.
Psychopharmacology (Berl). 2023 Mar;240(3):623-635. doi: 10.1007/s00213-022-06227-0. Epub 2022 Sep 3.
Reward-seeking in the world is driven by cues that can have ambiguous predictive and motivational value. To produce adaptive, flexible reward-seeking, it is necessary to exploit occasion setters, other distinct features in the environment, to resolve the ambiguity of Pavlovian reward-paired cues. Despite this, very little research has investigated the neurobiological underpinnings of occasion setting, and as a result little is known about which brain regions are critical for occasion setting. To address this, we exploited a recently developed task that was amenable to neurobiological inquiry where a conditioned stimulus is only predictive of reward delivery if preceded in time by the non-overlapping presentation of a separate cue-an occasion setter. This task required male rats to maintain and link cue-triggered expectations across time to produce adaptive reward-seeking. We interrogated the contributions of the basolateral amygdala and orbitofrontal cortex to occasion setting as these regions are thought to be critical for the computation and exploitation of state value, respectively. Reversible inactivation of either structure prior to the occasion-setting task resulted in a profound inability of rats to use the occasion setter to guide reward-seeking. In contrast, inactivation of the dorsal hippocampus, a region fundamental for context-specific responding was without effect nor did inactivation of the basolateral amygdala or orbitofrontal cortex in a standard Pavlovian conditioning preparation affect conditioned responding. We conclude that neural activity within the orbitofrontal cortex and basolateral amygdala circuit is necessary to update and resolve ambiguity in the environment to promote cue-driven reward-seeking.
世界上的奖励寻求是由具有模糊预测和激励价值的线索驱动的。为了产生适应性强、灵活的奖励寻求，有必要利用环境中的其他明显特征来解决条件反射奖励配对线索的模糊性。尽管如此，很少有研究调查过环境线索设定的神经生物学基础，因此，对于哪些大脑区域对环境线索设定至关重要，人们知之甚少。为了解决这个问题，我们利用了一种最近开发的任务，该任务适合神经生物学研究，其中条件刺激只有在时间上由另一个线索（即环境线索设定者）的非重叠呈现之前才可以预测奖励的传递。这个任务要求雄性大鼠在时间上维持和链接线索触发的期望，以产生适应性的奖励寻求。我们研究了外侧杏仁核和眶额皮质对环境线索设定的贡献，因为这两个区域分别被认为是对状态价值的计算和利用至关重要的。在环境线索设定任务之前可逆地失活这两个结构，会导致大鼠完全无法利用环境线索设定者来指导奖励寻求。相比之下，背侧海马体的失活（对于特定情境的反应至关重要的区域）没有影响，在标准的条件反射准备过程中，外侧杏仁核或眶额皮质的失活也不会影响条件反应。我们得出结论，眶额皮质和外侧杏仁核回路中的神经活动对于更新和解决环境中的模糊性以促进线索驱动的奖励寻求是必要的。
