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).

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.

Metrics

  • 1,881
    views
  • 345
    downloads
  • 24
    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. 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

Share this article

https://doi.org/10.7554/eLife.41542

Further reading

    1. Immunology and Inflammation
    2. Neuroscience
    Yuedan Wang, Ying Li ... Xuan Xiao
    Research Article

    Acute retinal ischemia and ischemia-reperfusion injury are the primary causes of retinal neural cell death and vision loss in retinal artery occlusion (RAO). The absence of an accurate mouse model for simulating the retinal ischemic process has hindered progress in developing neuroprotective agents for RAO. We developed a unilateral pterygopalatine ophthalmic artery occlusion (UPOAO) mouse model using silicone wire embolization combined with carotid artery ligation. The survival of retinal ganglion cells and visual function were evaluated to determine the duration of ischemia. Immunofluorescence staining, optical coherence tomography, and haematoxylin and eosin staining were utilized to assess changes in major neural cell classes and retinal structure degeneration at two reperfusion durations. Transcriptomics was employed to investigate alterations in the pathological process of UPOAO following ischemia and reperfusion, highlighting transcriptomic differences between UPOAO and other retinal ischemia-reperfusion models. The UPOAO model successfully replicated the acute interruption of retinal blood supply observed in RAO. 60 min of Ischemia led to significant loss of major retinal neural cells and visual function impairment. Notable thinning of the inner retinal layer, especially the ganglion cell layer, was evident post-UPOAO. Temporal transcriptome analysis revealed various pathophysiological processes related to immune cell migration, oxidative stress, and immune inflammation during the non-reperfusion and reperfusion periods. A pronounced increase in microglia within the retina and peripheral leukocytes accessing the retina was observed during reperfusion periods. Comparison of differentially expressed genes (DEGs) between the UPOAO and high intraocular pressure models revealed specific enrichments in lipid and steroid metabolism-related genes in the UPOAO model. The UPOAO model emerges as a novel tool for screening pathogenic genes and promoting further therapeutic research in RAO.

    1. Computational and Systems Biology
    2. Neuroscience
    Megan E Farquhar, Qianqian Yang, Viktor Vegh
    Research Article

    Diffusional kurtosis imaging (DKI) is a methodology for measuring the extent of non-Gaussian diffusion in biological tissue, which has shown great promise in clinical diagnosis, treatment planning, and monitoring of many neurological diseases and disorders. However, robust, fast, and accurate estimation of kurtosis from clinically feasible data acquisitions remains a challenge. In this study, we first outline a new accurate approach of estimating mean kurtosis via the sub-diffusion mathematical framework. Crucially, this extension of the conventional DKI overcomes the limitation on the maximum b-value of the latter. Kurtosis and diffusivity can now be simply computed as functions of the sub-diffusion model parameters. Second, we propose a new fast and robust fitting procedure to estimate the sub-diffusion model parameters using two diffusion times without increasing acquisition time as for the conventional DKI. Third, our sub-diffusion-based kurtosis mapping method is evaluated using both simulations and the Connectome 1.0 human brain data. Exquisite tissue contrast is achieved even when the diffusion encoded data is collected in only minutes. In summary, our findings suggest robust, fast, and accurate estimation of mean kurtosis can be realised within a clinically feasible diffusion-weighted magnetic resonance imaging data acquisition time.