1. Neuroscience

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
https://doi.org/10.7554/eLife.78912
Share this article
Cite this article
  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
  2. Download BibTeX
  3. Download .RIS

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.

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.

Metrics

  • 1,207
    views
  • 299
    downloads
  • 9
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  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

Share this article

https://doi.org/10.7554/eLife.78912

Categories and tags

Research organism

Further reading

    1. Neuroscience

    Risk of punishment influences discrete and coordinated encoding of reward-guided actions by prefrontal cortex and VTA neurons

    Junchol Park, Bita Moghaddam
    Research Article Updated

    Actions motivated by rewards are often associated with risk of punishment. Little is known about the neural representation of punishment risk during reward-seeking behavior. We modeled this circumstance in rats by designing a task where actions were consistently rewarded but probabilistically punished. Spike activity and local field potentials were recorded during task performance simultaneously from VTA and mPFC, two reciprocally connected regions implicated in reward-seeking and aversive behaviors. At the single unit level, we found that ensembles of putative dopamine and non-dopamine VTA neurons and mPFC neurons encode the relationship between action and punishment. At the network level, we found that coherent theta oscillations synchronize VTA and mPFC in a bottom-up direction, effectively phase-modulating the neuronal spike activity in the two regions during punishment-free actions. This synchrony declined as a function of punishment probability, suggesting that during reward-seeking actions, risk of punishment diminishes VTA-driven neural synchrony between the two regions.

    1. Neuroscience

    Cognition: When working memory works for our goals

    Jacob A Miller
    Insight

    When navigating environments with changing rules, human brain circuits flexibly adapt how and where we retain information to help us achieve our immediate goals.

    1. Neuroscience

    Stimulus representation in human frontal cortex supports flexible control in working memory

    Zhujun Shao, Mengya Zhang, Qing Yu
    Research Article

    When holding visual information temporarily in working memory (WM), the neural representation of the memorandum is distributed across various cortical regions, including visual and frontal cortices. However, the role of stimulus representation in visual and frontal cortices during WM has been controversial. Here, we tested the hypothesis that stimulus representation persists in the frontal cortex to facilitate flexible control demands in WM. During functional MRI, participants flexibly switched between simple WM maintenance of visual stimulus or more complex rule-based categorization of maintained stimulus on a trial-by-trial basis. Our results demonstrated enhanced stimulus representation in the frontal cortex that tracked demands for active WM control and enhanced stimulus representation in the visual cortex that tracked demands for precise WM maintenance. This differential frontal stimulus representation traded off with the newly-generated category representation with varying control demands. Simulation using multi-module recurrent neural networks replicated human neural patterns when stimulus information was preserved for network readout. Altogether, these findings help reconcile the long-standing debate in WM research, and provide empirical and computational evidence that flexible stimulus representation in the frontal cortex during WM serves as a potential neural coding scheme to accommodate the ever-changing environment.