A prospective code for value in the serotonin system

Emerson F. Harkin (), Cooper D. Grossman, Jeremiah Y. Cohen, Jean-Claude Béïque () and Richard Naud
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Emerson F. Harkin: University of Ottawa
Cooper D. Grossman: California Institute of Technology
Jeremiah Y. Cohen: Allen Institute for Neural Dynamics
Jean-Claude Béïque: University of Ottawa
Richard Naud: University of Ottawa

Nature, 2025, vol. 641, issue 8064, 952-959

Abstract: Abstract The in vivo responses of dorsal raphe nucleus serotonin neurons to emotionally salient stimuli are a puzzle1. Existing theories centring on reward2, surprise3, salience4 and uncertainty5 individually account for some aspects of serotonergic activity but not others. Merging ideas from reinforcement learning theory6 with recent insights into the filtering properties of the dorsal raphe nucleus7, here we find a unifying perspective in a prospective code for value. This biological code for near-future reward explains why serotonin neurons are activated by both rewards and punishments3,4,8–13, and why these neurons are more strongly activated by surprising rewards but have no such surprise preference for punishments3,9—observations that previous theories have failed to reconcile. Finally, our model quantitatively predicts in vivo population activity better than previous theories. By reconciling previous theories and establishing a precise connection with reinforcement learning, our work represents an important step towards understanding the role of serotonin in learning and behaviour.

Date: 2025
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DOI: 10.1038/s41586-025-08731-7

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