Generality and opponency of rostromedial tegmental (RMTg) roles in valence processing

  1. Hao Li
  2. Dominika Pullmann
  3. Jennifer Y Cho
  4. Maya Eid
  5. Thomas C Jhou  Is a corresponding author
  1. Medical University of South Carolina, United States

Abstract

The rostromedial tegmental nucleus (RMTg), a GABAergic afferent to midbrain dopamine (DA) neurons, has been hypothesized to be broadly activated by aversive stimuli. However, this encoding pattern has only been demonstrated for a limited number of stimuli, and the RMTg influence on ventral tegmental (VTA) responses to aversive stimuli is untested. Here, we found that RMTg neurons are broadly excited by aversive stimuli of different sensory modalities and inhibited by reward-related stimuli. These stimuli include visual, auditory, somatosensory and chemical aversive stimuli, as well as “opponent” motivational states induced by removal of sustained rewarding or aversive stimuli. These patterns are consistent with broad encoding of negative valence in a subset of RMTg neurons. We further found that valence-encoding RMTg neurons preferentially project to the DA-rich VTA versus other targets, and excitotoxic RMTg lesions greatly reduce aversive stimulus-induced inhibitions in VTA neurons, particularly putative DA neurons, while also impairing conditioned place aversion to multiple aversive stimuli. Together, our findings indicate a broad RMTg role in encoding aversion and driving VTA responses and behavior.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files.

Article and author information

Author details

  1. Hao Li

    Department of Neuroscience, Medical University of South Carolina, Charleston, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Dominika Pullmann

    Department of Neuroscience, Medical University of South Carolina, Charleston, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Jennifer Y Cho

    Department of Neuroscience, Medical University of South Carolina, Charleston, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Maya Eid

    Department of Neuroscience, Medical University of South Carolina, Charleston, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Thomas C Jhou

    Department of Neuroscience, Medical University of South Carolina, Charleston, United States
    For correspondence
    jhou@musc.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8811-0156

Funding

National Institutes of Health (R01 DA037327)

  • Thomas C Jhou

National Institutes of Health (R21 DA032898)

  • Thomas C Jhou

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 conducted under the National Institutes of Health Guide for the Care and Use of Laboratory Animals, and all protocols were approved by Medical University of South Carolina Institutional Animal Care and Use Committee (protocol #3522).

Reviewing Editor

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

Publication history

  1. Received: August 29, 2018
  2. Accepted: January 4, 2019
  3. Accepted Manuscript published: January 22, 2019 (version 1)
  4. Version of Record published: February 4, 2019 (version 2)

Copyright

© 2019, Li 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. Hao Li
  2. Dominika Pullmann
  3. Jennifer Y Cho
  4. Maya Eid
  5. Thomas C Jhou
(2019)
Generality and opponency of rostromedial tegmental (RMTg) roles in valence processing
eLife 8:e41542.
https://doi.org/10.7554/eLife.41542
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