Disruption of model-based decision making by silencing of serotonin neurons in the dorsal raphe nucleus
Disruption of model-based decision making by silencing of serotonin neurons in the dorsal raphe nucleus
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DOI：
10.1016/j.cub.2021.03.048
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发表时间：
2021-06-07
期刊：
影响因子：
9.2
通讯作者：
Yoshioka, Mitsuhiro
中科院分区：
文献类型：
--
作者：
Ohmura, Yu;Iwami, Kentaro;Yoshioka, Mitsuhiro
适应不断变化的环境条件需要对未来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。(1-3)在稳定的环境中，对行为及其后果的广泛经验导致了从基于模型的策略到无模型策略的转变，由此行为选择主要由积极和消极结果的回顾性经验决定。在人类和动物研究中，受试者被要求推测隐含的信息，并在多个会话中调整行为反应，指出了中枢神经系统在基于模型的决策中的作用。(4-8)然而，为了直接测试β-肾上腺素能活性和基于模型的决策之间的因果关系，在一次性测试中需要β-肾上腺素能活性的阶段特异性操纵，其中通过试错的学习被中和。此外，负责这种效果的多巴胺能起源尚未确定。在此，我们证明了中缝背核中5-羟色胺神经元的光遗传学沉默，而不是中缝中核中的5-羟色胺神经元，破坏了锂诱导的结果贬值任务中基于模型的决策。（9 - 11）我们的数据表明，多巴胺能行为效应不是由于增加的运动活动、抗焦虑作用或工作记忆缺陷。我们的研究结果提供了深入的神经机制之间的神经加权模型和基于模型的策略。
Adaptingto changing environmentalconditions requires a prospective inferenceof future actionsandtheir consequences, a strategy alsoknownasmodel-baseddecisionmaking.(1-3) In stable environments, extensive experience of actions and their consequences leads to a shift fromamodel-based to amodel-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 overmultiple sessions, point to a role for the central serotonergic systeminmodel-based decision making.(4-8) 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.(9-11) 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.