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Neuropsychopharmacology. 2018 May;43(6):1425-1435. doi: 10.1038/npp.2017.304. Epub 2018 Jan 3.

The Protective Action Encoding of Serotonin Transients in the Human Brain.

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Department of Engineering Mathematics, School of Computer Science, Electrical and Electronic Engineering, and Engineering Mathematics, University of Bristol, Bristol, UK.
Department of Physiology and Pharmacology, Wake Forest School of Medicine, Winston-Salem, NC, USA.
Department of Neurosurgery, Wake Forest School of Medicine, Winston-Salem, NC, USA.
Virginia Tech Carilion Research Institute, Virginia Tech, Roanoke, VA, USA.
Helen Wills Neuroscience Institute, University of California, Berkeley, CA, USA.
Department of Psychiatry & Behavioral Sciences, University of Washington, Seattle, WA, USA.
Department of Pharmacology, University of Washington, Seattle, WA, USA.
The Gatsby Computational Neuroscience Unit, University College London, London, UK.
Department of Physics, Virginia Tech, Blacksburg, VA, USA.
Wellcome Trust Centre for Neuroimaging, University College London, London, UK.


The role of serotonin in human brain function remains elusive due, at least in part, to our inability to measure rapidly the local concentration of this neurotransmitter. We used fast-scan cyclic voltammetry to infer serotonergic signaling from the striatum of 14 brains of human patients with Parkinson's disease. Here we report these novel measurements and show that they correlate with outcomes and decisions in a sequential investment game. We find that serotonergic concentrations transiently increase as a whole following negative reward prediction errors, while reversing when counterfactual losses predominate. This provides initial evidence that the serotonergic system acts as an opponent to dopamine signaling, as anticipated by theoretical models. Serotonin transients on one trial were also associated with actions on the next trial in a manner that correlated with decreased exposure to poor outcomes. Thus, the fluctuations observed for serotonin appear to correlate with the inhibition of over-reactions and promote persistence of ongoing strategies in the face of short-term environmental changes. Together these findings elucidate a role for serotonin in the striatum, suggesting it encodes a protective action strategy that mitigates risk and modulates choice selection particularly following negative environmental events.

[Available on 2019-05-01]

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