Disruption of model-based decision making by silencing of serotonin neurons in the dorsal raphe nucleus

Adapting to changing environmental conditions requires a prospective inference of future actions and their consequences, a strategy also known as model-based decision making.^1-3 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.^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.