Cheng Yifeng, Magnard Robin, Langdon Angela J, Lee Daeyeol, Janak Patricia H
Department Psychological and Brain Sciences, Krieger School of Arts and Sciences, Johns Hopkins University, Baltimore, MD, USA.
Kavli Neuroscience Discovery Institute, Johns Hopkins University, Baltimore, MD, USA.
Sci Adv. 2025 Apr 4;11(14):eadt0200. doi: 10.1126/sciadv.adt0200. Epub 2025 Apr 2.
Value-based decision-making relies on the striatum, where neural plasticity can be altered by chronic ethanol (EtOH) exposure, but the effects of such plasticity on striatal neural dynamics during decision-making remain unclear. This study investigated the long-term impacts of EtOH on reward-driven decision-making and striatal neurocomputations in male and female rats using a dynamic probabilistic reversal learning task. Following a prolonged withdrawal period, EtOH-exposed male rats exhibited deficits in adaptability and exploratory behavior, with aberrant outcome-driven value updating that heightened preference for chosen action. These behavioral changes were linked to altered neural activity in the dorsomedial striatum (DMS), where EtOH increased outcome-related encoding and decreased choice-related encoding. In contrast, female rats showed minimal behavioral changes with distinct EtOH-evoked alterations of neural activity, revealing significant sex differences in the impact of chronic EtOH. Our findings underscore the impact of chronic EtOH exposure on adaptive decision-making, revealing enduring changes in neurocomputational processes in the striatum underlying cognitive deficits that differ by sex.
基于价值的决策依赖于纹状体，长期乙醇（EtOH）暴露可改变其神经可塑性，但这种可塑性对决策过程中纹状体神经动力学的影响仍不清楚。本研究使用动态概率反转学习任务，研究了EtOH对雄性和雌性大鼠奖励驱动决策和纹状体神经计算的长期影响。在延长的戒断期后，暴露于EtOH的雄性大鼠在适应性和探索行为方面表现出缺陷，异常的结果驱动价值更新增加了对所选行动的偏好。这些行为变化与背内侧纹状体（DMS）的神经活动改变有关，在DMS中，EtOH增加了与结果相关的编码并减少了与选择相关的编码。相比之下，雌性大鼠表现出最小的行为变化，伴有EtOH诱发的明显神经活动改变，揭示了慢性EtOH影响的显著性别差异。我们的研究结果强调了慢性EtOH暴露对适应性决策的影响，揭示了纹状体神经计算过程中的持久变化，这些变化是认知缺陷的基础，且存在性别差异。
