Learning of probabilistic punishment as a model of anxiety produces changes in action but not punisher encoding in the dmPFC and VTA

  1. David S Jacobs
  2. Madeleine C Allen
  3. Junchol Park
  4. Bita Moghaddam  Is a corresponding author
  1. Oregon Health and Science University, United States
  2. Janelia Research Campus, United States

Abstract

Previously, we developed a novel model for anxiety during motivated behavior by training rats to perform a task where actions executed to obtain a reward were probabilistically punished and observed that after learning, neuronal activity in the ventral tegmental area (VTA) and dorsomedial prefrontal cortex (dmPFC) represent the relationship between action and punishment risk (Park & Moghaddam, 2017). Here we used male and female rats to expand on the previous work by focusing on neural changes in the dmPFC and VTA that were associated with the learning of probabilistic punishment, and anxiolytic treatment with diazepam after learning. We find that adaptive neural responses of dmPFC and VTA during the learning of anxiogenic contingencies are independent from the punisher experience and occur primarily during the peri-action and reward period. Our results also identify peri-action ramping of VTA neural calcium activity, and VTA-dmPFC correlated activity, as potential markers for the anxiolytic properties of diazepam.

Data availability

Data generated for analyses has been deposited on Dryad. Source code for analysis is available on github (https://github.com/MoghaddamLab).

The following data sets were generated

Article and author information

Author details

  1. David S Jacobs

    Department of Behavioral Neuroscience, Oregon Health and Science University, Portland, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Madeleine C Allen

    Department of Behavioral Neuroscience, Oregon Health and Science University, Portland, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Junchol Park

    Howard Hughes Medical Institute, Janelia Research Campus, Ashburn, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Bita Moghaddam

    Department of Behavioral Neuroscience, Oregon Health and Science University, Portland, United States
    For correspondence
    bita@ohsu.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5205-417X

Funding

National Institute of Mental Health (MH115026)

  • Bita Moghaddam

National Institute on Drug Abuse (DA007262)

  • David S Jacobs
  • Madeleine C Allen

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 experimental procedures were approved by the OHSU Institutional Animal Use and Care Committee (Protocol #: 15065884) and were conducted in accordance with National Institutes of Health Guide for the Care and Use of Laboratory Animals.

Reviewing Editor

  1. Geoffrey Schoenbaum, National Institute on Drug Abuse, National Institutes of Health, United States

Publication history

  1. Preprint posted: March 29, 2022 (view preprint)
  2. Received: March 29, 2022
  3. Accepted: August 30, 2022
  4. Accepted Manuscript published: September 14, 2022 (version 1)
  5. Version of Record published: September 30, 2022 (version 2)

Copyright

© 2022, Jacobs 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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  1. David S Jacobs
  2. Madeleine C Allen
  3. Junchol Park
  4. Bita Moghaddam
(2022)
Learning of probabilistic punishment as a model of anxiety produces changes in action but not punisher encoding in the dmPFC and VTA
eLife 11:e78912.
https://doi.org/10.7554/eLife.78912

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