Department of Neuropharmacology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, N15 W7 Kita-ku, Sapporo 060-8638, Japan.
Hokkaido University School of Medicine, N15 W7 Kita-ku, Sapporo 060-8638, Japan.
Curr Biol. 2021 Jun 7;31(11):2446-2454.e5. doi: 10.1016/j.cub.2021.03.048. Epub 2021 Apr 9.
Adapting to changing environmental conditions requires a prospective inference of future actions and their consequences, a strategy also known as model-based decision making. In stable environments, extensive experience of actions and their consequences leads to a shift from a model-based to a model-free strategy, whereby behavioral selection is primarily governed by retrospective experiences of positive and negative outcomes. Human and animal studies, where subjects are required to speculate about implicit information and adjust behavioral responses over multiple sessions, point to a role for the central serotonergic system in model-based decision making. However, to directly test a causal relationship between serotonergic activity and model-based decision making, phase-specific manipulation of serotonergic activity is needed in a one-shot test, where learning by trial and error is neutralized. Moreover, the serotonergic origin responsible for this effect is yet to be determined. Herein, we demonstrate that optogenetic silencing of serotonin neurons in the dorsal raphe nucleus, but not in the median raphe nucleus, disrupts model-based decision making in lithium-induced outcome devaluation tasks. Our data indicate that the serotonergic behavioral effects are not due to increased locomotor activity, anxiolytic effects, or working memory deficits. Our findings provide insights into the neural mechanisms underlying neural weighting between model-free and model-based strategies.
适应不断变化的环境条件需要对未来的行动及其后果进行前瞻性推断，这也是一种基于模型的决策策略。在稳定的环境中，对行动及其后果的广泛经验会导致从基于模型的策略向无模型策略的转变，从而使行为选择主要由积极和消极结果的回顾性经验决定。人类和动物研究表明，在需要推测隐含信息并在多个会话中调整行为反应的情况下，中枢 5-羟色胺能系统在基于模型的决策中起作用。然而，要直接测试 5-羟色胺能活动与基于模型的决策之间的因果关系，需要在一次性测试中对 5-羟色胺能活动进行特定相位的操纵，从而消除通过试错进行的学习。此外，负责这种效果的 5-羟色胺起源仍有待确定。在此，我们证明，光遗传学沉默背侧中缝核中的 5-羟色胺神经元，但不沉默中缝核中的 5-羟色胺神经元，会破坏锂诱导的结果贬值任务中的基于模型的决策。我们的数据表明，5-羟色胺的行为效应不是由于运动活动增加、抗焦虑作用或工作记忆缺陷引起的。我们的发现为基于模型的策略和无模型策略之间的神经权重的神经机制提供了深入的了解。
