Serotonin is implicated in mood and affective disorders. However, growing evidence suggests that a core endogenous role is to promote flexible adaptation to changes in the causal structure of the environment, through behavioral inhibition and enhanced plasticity. We used long-term photometric recordings in mice to study a population of dorsal raphe serotonin neurons, whose activity we could link to normal reversal learning using pharmacogenetics. We found that these neurons are activated by both positive and negative prediction errors, and thus report signals similar to those proposed to promote learning in conditions of uncertainty. Furthermore, by comparing the cue responses of serotonin and dopamine neurons, we found differences in learning rates that could explain the importance of serotonin in inhibiting perseverative responding. Our findings show how the activity patterns of serotonin neurons support a role in cognitive flexibility, and suggest a revised model of dopamine–serotonin opponency with potential clinical implications.
Bibliographical noteFunding Information:
We thank R M Costa and J J Paton Labs for TH-Cre mice, Susana Dias and Sérgio Casimiro for histology and immunohistochemistry assistance, and Dario Sarra for running behavioral experiments for a few days. We also thank C Poo, B V Atallah, M Murakami, G Agarwal and J J Paton for comments on a previous version of the manuscript, and all members of the Systems Neuroscience Lab and the Champalimaud Research for useful discussions and feedback during the development of this project. This work was supported by the Fundação para a Ciência e Tecnologia (fellowship SFRH/BD/43072/ 2008 to SM), Human Frontier Science Program (fellowship LT000881/2011L to EL), European Research Council (Advanced Investigator Grants 250334 and 671251 to ZFM) and Champalimaud Foundation (ZFM). Fundação para a Ciência e a Tecnologia SFRH/BD/43072/2008 Sara Matias Human Frontier Science Program LT00088/011L Eran Lottem European Research Council 250334 Zachary F Mainen Champalimaud Foundation Zachary F Mainen European Research Council 671251 Zachary F Mainen The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
© Matias et al.