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Technology Development Initiative – Paper of the Month – July 2024

A portion of a figure from this study. Image copyright: Nature.

Image copyright: Nature.

Unlocking opioid neuropeptide dynamics with genetically-encoded biosensors

Published in Nature Neuroscience.

Authors

Lin Tian, Chunyang Dong, Raajaram Gowrishankar, Yihan Jin, Xinyi He, Achla Gupta, Huikun Wang, Nilufer Atasoy, Rodolfo Flores-Garcia, Karan Mahe, Ruqiang Liang, Grace Or, Darren Lo, Qingtao Sun, Jennifer Whistler, Bo Li, Ivone Gomes, Hugo Tejeda, Deniz Atasoy, Lakshmi Devi, Michael Bruchas, Matthew Banghart

Paper presented by Dr. Renata Marchette and selected by the NIDA TDI Paper of the Month Committee

Publication Brief Description

Studies in opioid neuropeptide systems have historically faced challenges due to a lack of sensitive experimental tools capable of facilitating the understanding of the complexity and diversity of endogenous opioid signaling in a circuit-specific manner. To address this, researchers have developed a class of genetically encoded opioid peptide indicators: κLight, δLight, and µLight, based on κ, δ, and µ opioid receptors, respectively. These sensors respond to both endogenous opioid neuropeptides and exogenous drugs targeting the three receptors, detecting and differentiating conformational changes in the receptors. κLight and δLight, in particular, can detect rapid opioid peptide release in a subregion-specific manner in awake and freely behaving mice. These sensors are invaluable for understanding endogenous opioid transmission in contexts such as drug addiction, withdrawal, and motivated behavior.


Dong, Chunyang; Gowrishankar, Raajaram; Jin, Yihan; He, Xinyi Jenny; Gupta, Achla; Wang, Huikun; Sayar-Atasoy, Nilüfer; Flores, Rodolfo J; Mahe, Karan; Tjahjono, Nikki; Liang, Ruqiang; Marley, Aaron; Mizuno, Grace Or; Lo, Darren K; Sun, Qingtao; Whistler, Jennifer L; Li, Bo; Gomes, Ivone; Zastrow, Mark Von; Tejeda, Hugo A; Atasoy, Deniz; Devi, Lakshmi A; Bruchas, Michael R; Banghart, Matthew R; Tian, Lin

Unlocking opioid neuropeptide dynamics with genetically encoded biosensors Journal Article

In: Nat Neurosci, 2024, ISSN: 1546-1726.

Abstract | Links

@article{pmid39009835,
title = {Unlocking opioid neuropeptide dynamics with genetically encoded biosensors},
author = {Chunyang Dong and Raajaram Gowrishankar and Yihan Jin and Xinyi Jenny He and Achla Gupta and Huikun Wang and Nilüfer Sayar-Atasoy and Rodolfo J Flores and Karan Mahe and Nikki Tjahjono and Ruqiang Liang and Aaron Marley and Grace Or Mizuno and Darren K Lo and Qingtao Sun and Jennifer L Whistler and Bo Li and Ivone Gomes and Mark Von Zastrow and Hugo A Tejeda and Deniz Atasoy and Lakshmi A Devi and Michael R Bruchas and Matthew R Banghart and Lin Tian},
url = {https://pubmed.ncbi.nlm.nih.gov/39009835/},
doi = {10.1038/s41593-024-01697-1},
issn = {1546-1726},
year = {2024},
date = {2024-07-01},
urldate = {2024-07-01},
journal = {Nat Neurosci},
abstract = {Neuropeptides are ubiquitous in the nervous system. Research into neuropeptides has been limited by a lack of experimental tools that allow for the precise dissection of their complex and diverse dynamics in a circuit-specific manner. Opioid peptides modulate pain, reward and aversion and as such have high clinical relevance. To illuminate the spatiotemporal dynamics of endogenous opioid signaling in the brain, we developed a class of genetically encoded fluorescence sensors based on kappa, delta and mu opioid receptors: κLight, δLight and µLight, respectively. We characterized the pharmacological profiles of these sensors in mammalian cells and in dissociated neurons. We used κLight to identify electrical stimulation parameters that trigger endogenous opioid release and the spatiotemporal scale of dynorphin volume transmission in brain slices. Using in vivo fiber photometry in mice, we demonstrated the utility of these sensors in detecting optogenetically driven opioid release and observed differential opioid release dynamics in response to fearful and rewarding conditions.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}

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Neuropeptides are ubiquitous in the nervous system. Research into neuropeptides has been limited by a lack of experimental tools that allow for the precise dissection of their complex and diverse dynamics in a circuit-specific manner. Opioid peptides modulate pain, reward and aversion and as such have high clinical relevance. To illuminate the spatiotemporal dynamics of endogenous opioid signaling in the brain, we developed a class of genetically encoded fluorescence sensors based on kappa, delta and mu opioid receptors: κLight, δLight and µLight, respectively. We characterized the pharmacological profiles of these sensors in mammalian cells and in dissociated neurons. We used κLight to identify electrical stimulation parameters that trigger endogenous opioid release and the spatiotemporal scale of dynorphin volume transmission in brain slices. Using in vivo fiber photometry in mice, we demonstrated the utility of these sensors in detecting optogenetically driven opioid release and observed differential opioid release dynamics in response to fearful and rewarding conditions.

Close

  • https://pubmed.ncbi.nlm.nih.gov/39009835/
  • doi:10.1038/s41593-024-01697-1

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