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      An effect of serotonergic stimulation on learning rates for rewards apparent after long intertrial intervals

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          Abstract

          Serotonin has widespread, but computationally obscure, modulatory effects on learning and cognition. Here, we studied the impact of optogenetic stimulation of dorsal raphe serotonin neurons in mice performing a non-stationary, reward-driven decision-making task. Animals showed two distinct choice strategies. Choices after short inter-trial-intervals (ITIs) depended only on the last trial outcome and followed a win-stay-lose-switch pattern. In contrast, choices after long ITIs reflected outcome history over multiple trials, as described by reinforcement learning models. We found that optogenetic stimulation during a trial significantly boosted the rate of learning that occurred due to the outcome of that trial, but these effects were only exhibited on choices after long ITIs. This suggests that serotonin neurons modulate reinforcement learning rates, and that this influence is masked by alternate, unaffected, decision mechanisms. These results provide insight into the role of serotonin in treating psychiatric disorders, particularly its modulation of neural plasticity and learning.

          Abstract

          Serotonin (5-HT) plays many important roles in reward, punishment, patience and beyond, and optogenetic stimulation of 5-HT neurons has not crisply parsed them. The authors report a novel analysis of a reward-based decision-making experiment, and show that 5-HT stimulation increases the learning rate, but only on a select subset of choices.

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          Learning to predict by the methods of temporal differences

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            A framework for mesencephalic dopamine systems based on predictive Hebbian learning.

            We develop a theoretical framework that shows how mesencephalic dopamine systems could distribute to their targets a signal that represents information about future expectations. In particular, we show how activity in the cerebral cortex can make predictions about future receipt of reward and how fluctuations in the activity levels of neurons in diffuse dopamine systems above and below baseline levels would represent errors in these predictions that are delivered to cortical and subcortical targets. We present a model for how such errors could be constructed in a real brain that is consistent with physiological results for a subset of dopaminergic neurons located in the ventral tegmental area and surrounding dopaminergic neurons. The theory also makes testable predictions about human choice behavior on a simple decision-making task. Furthermore, we show that, through a simple influence on synaptic plasticity, fluctuations in dopamine release can act to change the predictions in an appropriate manner.
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              Relative and absolute strength of response as a function of frequency of reinforcement.

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                Author and article information

                Contributors
                kiigaya@gatsby.ucl.ac.uk
                Journal
                Nat Commun
                Nat Commun
                Nature Communications
                Nature Publishing Group UK (London )
                2041-1723
                26 June 2018
                26 June 2018
                2018
                : 9
                : 2477
                Affiliations
                [1 ]ISNI 0000000121901201, GRID grid.83440.3b, Gatsby Computational Neuroscience Unit, , University College London, ; 25 Howland Street, London, W1T 4JG UK
                [2 ]ISNI 0000000121901201, GRID grid.83440.3b, Max Planck UCL Centre for Computational Psychiatry and Ageing Research, ; Russell Square House, 10-12 Russell Square, London, WC1B 5EH UK
                [3 ]ISNI 0000000107068890, GRID grid.20861.3d, Division of Humanities and Social Sciences, , California Institute of Technology, ; 1200 E California Blvd, Pasadena, CA 91125 USA
                [4 ]ISNI 0000 0004 0453 9636, GRID grid.421010.6, Champalimaud Research, , Champalimaud Centre for the Unknown, ; Avenida Brasília, 1400-038 Lisbon, Portugal
                Author information
                http://orcid.org/0000-0002-4748-8432
                http://orcid.org/0000-0003-3476-1839
                Article
                4840
                10.1038/s41467-018-04840-2
                6018802
                29946069
                2b37485f-92d9-46c1-a6d2-5f2013c6f8ae
                © The Author(s) 2018

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 4 December 2017
                : 22 May 2018
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