1. Neuroscience
Download icon

Synapse-specific Opioid Modulation of Thalamo-cortico-striatal Circuits

  1. William T Birdsong  Is a corresponding author
  2. Bart C Jongbloets
  3. Kim A Engeln
  4. Dong Wang
  5. Gregory Scherrer
  6. Tianyi Mao  Is a corresponding author
  1. Oregon Health and Science University, United States
  2. Stanford University, United States
Research Article
  • Cited 18
  • Views 2,772
  • Annotations
Cite this article as: eLife 2019;8:e45146 doi: 10.7554/eLife.45146

Abstract

The medial thalamus (MThal), anterior cingulate cortex (ACC) and striatum play important roles in affective-motivational pain processing and reward learning. Opioids affect both pain and reward through uncharacterized modulation of this circuitry. This study examined opioid actions on glutamate transmission between these brain regions in mouse. Mu-opioid receptor (MOR) agonists potently inhibited MThal inputs without affecting ACC inputs to individual striatal medium spiny neurons (MSNs). MOR activation also inhibited MThal inputs to the pyramidal neurons in the ACC. In contrast, delta-opioid receptor (DOR) agonists disinhibited ACC pyramidal neuron responses to MThal inputs by suppressing local feed-forward GABA signaling from parvalbumin-positive interneurons. As a result, DOR activation in the ACC facilitated poly-synaptic (thalamo-cortico-striatal) excitation of MSNs by MThal inputs. These results suggest that opioid effects on pain and reward may be shaped by the relative selectivity of opioid drugs to the specific circuit components.

Data availability

All data generated or analyzed during this study are included in the manuscript and supporting files. All code and data are deposited in https://gitlab.com/maolab/opi_syn_circuit. ecfa1f13.

Article and author information

Author details

  1. William T Birdsong

    Vollum Institute, Oregon Health and Science University, Portland, United States
    For correspondence
    wtbird@med.umich.edu
    Competing interests
    The authors declare that no competing interests exist.

  2. Bart C Jongbloets

    Vollum Institute, Oregon Health and Science University, Portland, United States
    Competing interests
    The authors declare that no competing interests exist.

  3. Kim A Engeln

    Vollum Institute, Oregon Health and Science University, Portland, United States
    Competing interests
    The authors declare that no competing interests exist.

  4. Dong Wang

    Department of Anesthesiology, Perioperative and Pain Medicine, Department of Molecular and Cellular Physiology, Department of Neurosurgery, Stanford University, Palo Alto, United States
    Competing interests
    The authors declare that no competing interests exist.

  5. Gregory Scherrer

    Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University, Palo Alto, United States
    Competing interests
    The authors declare that no competing interests exist.

  6. Tianyi Mao

    Vollum Institute, Oregon Health and Science University, Portland, United States
    For correspondence
    mao@ohsu.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3532-8319

Funding

National Institute of Neurological Disorders and Stroke (R01NS081071)

  • Tianyi Mao

New York Stem Cell Foundation

  • Gregory Scherrer

National Institute on Drug Abuse (R01DA042779)

  • William T Birdsong

National Institute on Drug Abuse (R01DA044481)

  • Gregory Scherrer

National Institute on Drug Abuse (R01NS106301)

  • Gregory Scherrer

National Institute of Neurological Disorders and Stroke (R01NS104944)

  • Tianyi Mao

National Institute of Neurological Disorders and Stroke (U01NS094247)

  • Tianyi Mao

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 approved by Oregon Health & Science University Institutional Animal Care and Use Committee (IACUC) and all experiments were performed strictly according the approved protocols. IACUC protocol IP00000955, and Institutional Biosafety Committee protocol IBC-10-40.

Reviewing Editor

  1. Olivier J Manzoni, Aix-Marseille University, INSERM, INMED, France

Publication history

  1. Received: January 14, 2019
  2. Accepted: May 15, 2019
  3. Accepted Manuscript published: May 17, 2019 (version 1)
  4. Version of Record published: May 29, 2019 (version 2)

Copyright

© 2019, Birdsong 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

  • 2,772
    Page views
  • 525
    Downloads
  • 18
    Citations

Article citation count generated by polling the highest count across the following sources: Scopus, Crossref, PubMed Central.

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)

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

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

Categories and tags

Research organism

Further reading

    1. Computational and Systems Biology
    2. Neuroscience

    The sleep-wake distribution contributes to the peripheral rhythms in PERIOD-2

    Marieke MB Hoekstra et al.
    Research Article Updated

    In the mouse, Period-2 (Per2) expression in tissues peripheral to the suprachiasmatic nuclei (SCN) increases during sleep deprivation and at times of the day when animals are predominantly awake spontaneously, suggesting that the circadian sleep-wake distribution directly contributes to the daily rhythms in Per2. We found support for this hypothesis by recording sleep-wake state alongside PER2 bioluminescence in freely behaving mice, demonstrating that PER2 bioluminescence increases during spontaneous waking and decreases during sleep. The temporary reinstatement of PER2-bioluminescence rhythmicity in behaviorally arrhythmic SCN-lesioned mice submitted to daily recurring sleep deprivations substantiates our hypothesis. Mathematical modeling revealed that PER2 dynamics can be described by a damped harmonic oscillator driven by two forces: a sleep-wake-dependent force and an SCN-independent circadian force. Our work underscores the notion that in peripheral tissues the clock gene circuitry integrates sleep-wake information and could thereby contribute to behavioral adaptability to respond to homeostatic requirements.

    1. Neuroscience

    Synaptic memory requires CaMKII

    Wucheng Tao et al.
    Research Article Updated

    Long-term potentiation (LTP) is arguably the most compelling cellular model for learning and memory. While the mechanisms underlying the induction of LTP (‘learning’) are well understood, the maintenance of LTP (‘memory’) has remained contentious over the last 20 years. Here, we find that Ca2+-calmodulin-dependent kinase II (CaMKII) contributes to synaptic transmission and is required LTP maintenance. Acute inhibition of CaMKII erases LTP and transient inhibition of CaMKII enhances subsequent LTP. These findings strongly support the role of CaMKII as a molecular storage device.

    1. Medicine
    2. Neuroscience

    Virtual mouse brain histology from multi-contrast MRI via deep learning

    Zifei Liang et al.
    Tools and Resources

    1H MRI maps brain structure and function non-invasively through versatile contrasts that exploit inhomogeneity in tissue micro-environments. Inferring histopathological information from MRI findings, however, remains challenging due to absence of direct links between MRI signals and cellular structures. Here, we show that deep convolutional neural networks, developed using co-registered multi-contrast MRI and histological data of the mouse brain, can estimate histological staining intensity directly from MRI signals at each voxel. The results provide three-dimensional maps of axons and myelin with tissue contrasts that closely mimics target histology and enhanced sensitivity and specificity compared to conventional MRI markers. Furthermore, the relative contribution of each MRI contrast within the networks can be used to optimize multi-contrast MRI acquisition. We anticipate our method to be a starting point for translation of MRI results into easy-to-understand virtual histology for neurobiologists and provide resources for validating novel MRI techniques.