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Distinct temporal difference error signals in dopamine axons in three regions of the striatum in a decision-making task

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Cite this article as: eLife 2020;9:e62390 doi: 10.7554/eLife.62390

Abstract

Different regions of the striatum regulate different types of behavior. However, how dopamine signals differ across striatal regions and how dopamine regulates different behaviors remain unclear. Here, we compared dopamine axon activity in the ventral, dorsomedial, and dorsolateral striatum, while mice performed a perceptual and value-based decision task. Surprisingly, dopamine axon activity was similar across all three areas. At a glance, the activity multiplexed different variables such as stimulus-associated values, confidence and reward feedback at different phases of the task. Our modeling demonstrates, however, that these modulations can be inclusively explained by moment-by-moment changes in the expected reward, i.e. the temporal difference error. A major difference between areas was the overall activity level of reward responses: reward responses in dorsolateral striatum were positively shifted, lacking inhibitory responses to negative prediction errors. The differences in dopamine signals put specific constraints on the properties of behaviors controlled by dopamine in these regions.

Data availability

A source code file has been provided for Figure 7. Fluorometry data has been deposited in Dryad available at: doi:10.5061/dryad.pg4f4qrmf.

The following data sets were generated

Article and author information

Author details

  1. Iku Tsutsui-Kimura

    Center for Brain Science, Molecular and Cellular Biology, Harvard University, Cambridge, United States
    Competing interests
    No competing interests declared.
  2. Hideyuki Matsumoto

    Center for Brain Science, Molecular and Cellular Biology, Harvard University, Cambridge, United States
    Competing interests
    No competing interests declared.
  3. Korleki Akiti

    Center for Brain Science, Molecular and Cellular Biology, Harvard University, Cambridge, United States
    Competing interests
    No competing interests declared.
  4. Melissa M Yamada

    Center for Brain Science, Molecular and Cellular Biology, Harvard University, Cambridge, United States
    Competing interests
    No competing interests declared.
  5. Naoshige Uchida

    Center for Brain Science, Harvard University, Cambridge, United States
    Competing interests
    Naoshige Uchida, Reviewing editor, eLife.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5755-9409
  6. Mitsuko Watabe-Uchida

    Center for Brain Science, Molecular and Cellular Biology, Harvard University, Cambridge, United States
    For correspondence
    mitsuko@mcb.harvard.edu
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7864-754X

Funding

Japan Society for the Promotion of Science

  • Iku Tsutsui-Kimura

Japan Society for the Promotion of Science

  • Hideyuki Matsumoto

National Institute of Mental Health (R01MH095953,R01MH101207,R01MH110404,R01NS108740)

  • Naoshige Uchida

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: All procedures were performed in accordance with the National Institutes of Health Guide for the Care and Use of Laboratory Animals and approved by the Harvard Animal Care and Use Committee (protocol #26-03). All surgeries were performed under aseptic conditions with animals anesthetized with isoflurane (1-2% at 0.5-1.0 l/min). Analgesia was administered pre (buprenorphine, 0.1 mg/kg, I.P) and postoperatively (ketoprofen, 5 mg/kg, I.P).

Reviewing Editor

  1. Joseph F Cheer, University of Maryland School of Medicine, United States

Publication history

  1. Received: August 23, 2020
  2. Accepted: December 18, 2020
  3. Accepted Manuscript published: December 21, 2020 (version 1)
  4. Version of Record published: December 29, 2020 (version 2)

Copyright

© 2020, Tsutsui-Kimura et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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