Synapse-specific Opioid Modulation of Thalamo-cortico-striatal Circuits
- Oregon Health and Science University, United States
- Stanford University, United States
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
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
- Olivier J Manzoni, Aix-Marseille University, INSERM, INMED, France
Publication history
- Received: January 14, 2019
- Accepted: May 15, 2019
- Accepted Manuscript published: May 17, 2019 (version 1)
- 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.
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Synapse-specific Opioid Modulation of Thalamo-cortico-striatal Circuits
eLife 8:e45146.
https://doi.org/10.7554/eLife.45146
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