1. Neuroscience
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Mechanism for differential recruitment of orbitostriatal transmission during actions and outcomes following chronic alcohol exposure

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Cite this article as: eLife 2021;10:e67065 doi: 10.7554/eLife.67065

Abstract

Psychiatric disease often produces symptoms that have divergent effects on neural activity. For example, in drug dependence, dysfunctional value-based decision-making and compulsive-like actions have been linked to hypo- and hyper-activity of orbital frontal cortex (OFC)-basal ganglia circuits, respectively, however, the underlying mechanisms are unknown. Here we show that alcohol exposed mice have enhanced activity in OFC terminals in dorsal striatum (OFC-DS) associated with actions, but reduced activity of the same terminals during periods of outcome retrieval, corresponding with a loss of outcome control over decision-making. Disrupted OFC-DS terminal activity was due to a dysfunction of dopamine-type 1 receptors on spiny projection neurons (D1R SPNs) that resulted in increased retrograde endocannabinoid (eCB) signaling at OFC-D1R SPN synapses reducing OFC-DS transmission. Blocking CB1 receptors restored OFC-DS activity in vivo and rescued outcome-based control over decision-making. These findings demonstrate a circuit-, synapse-, and computation specific mechanism gating OFC activity in alcohol exposed mice.

Data availability

All data generated or analyzed during this study are included in the manuscript and supporting files. Source data for all figures has been provided.

Article and author information

Author details

  1. Rafael Renteria

    Department of Psychology, University of California, San Diego, La Jolla, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6199-0293
  2. Christian Cazares

    The Neurosciences Graduate Program, University of California, San Diego, La Jolla, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8899-2109
  3. Emily T Baltz

    The Neurosciences Graduate Program, University of California, San Diego, La Jolla, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9770-3666
  4. Drew C Schreiner

    Department of Psychology, University of California, San Diego, La Jolla, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Ege A Yalcinbas

    The Neurosciences Graduate Program, University of California, San Diego, La Jolla, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9480-7192
  6. Thomas Steinkellner

    Department of Neurosciences, University of California, San Diego, La Jolla, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Thomas S Hnasko

    Department of Neurosciences, The Neurosciences Graduate Program, University of California, San Diego, La Jolla, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6176-8513
  8. Christina M Gremel

    Department of Psychology, The Neurosciences Graduate Program, University of California, San Diego, La Jolla, United States
    For correspondence
    cgremel@ucsd.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8710-0543

Funding

National Institutes of Health (AA026077-01A1)

  • Christina M Gremel

National Institutes of Health (F32 AA026776)

  • Rafael Renteria

National Science Foundation (NSF-GRFP DGE-2038238)

  • Emily T Baltz

National Science Foundation (NSF-GRFP DGE-1650112)

  • Christian Cazares

National Institutes of Health (F31 AA027439)

  • Drew C Schreiner

National Institutes of Health (R01DA036612)

  • Thomas S Hnasko

National Institutes of Health (R01NS106822)

  • Thomas S Hnasko

National Institutes of Health (T01BX003759)

  • Thomas S Hnasko

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

Ethics

Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All experiments were approved by the Institutional Animal Care and Use Committees of the University of California San Diego and experiments were conducted according to NIH guidelines.

Reviewing Editor

  1. Laura A Bradfield, University of Technology Sydney, Australia

Publication history

  1. Received: January 29, 2021
  2. Accepted: March 16, 2021
  3. Accepted Manuscript published: March 17, 2021 (version 1)
  4. Version of Record published: April 1, 2021 (version 2)

Copyright

© 2021, Renteria 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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