Development of a genetically encoded sensor for probing endogenous nociceptin opioid peptide release

Xuehan Zhou, Carrie Stine, Patricia Oliveira Prada, Debora Fusca, Kevin Assoumou, Jan Dernic, Musadiq A. Bhat, Ananya S. Achanta, Joseph C. Johnson, Amanda Loren Pasqualini, Sanjana Jadhav, Corinna A. Bauder, Lukas Steuernagel, Luca Ravotto, Dietmar Benke, Bruno Weber, Azra Suko, Richard D. Palmiter, Miriam Stoeber, Peter Kloppenburg, Jens C. Brüning, Michael R. Bruchas () and Tommaso Patriarchi ()
Additional contact information
Xuehan Zhou: University of Zürich
Carrie Stine: University of Washington
Patricia Oliveira Prada: Max Planck Institute for Metabolism Research
Debora Fusca: University of Cologne
Kevin Assoumou: University of Geneva
Jan Dernic: University of Zürich
Musadiq A. Bhat: University of Zürich
Ananya S. Achanta: University of Washington
Joseph C. Johnson: University of Washington
Amanda Loren Pasqualini: University of Washington
Sanjana Jadhav: University of Washington
Corinna A. Bauder: Max Planck Institute for Metabolism Research
Lukas Steuernagel: Max Planck Institute for Metabolism Research
Luca Ravotto: University of Zürich
Dietmar Benke: University of Zürich
Bruno Weber: University of Zürich
Azra Suko: University of Washington
Richard D. Palmiter: University of Washington
Miriam Stoeber: University of Geneva
Peter Kloppenburg: University of Cologne
Jens C. Brüning: Max Planck Institute for Metabolism Research
Michael R. Bruchas: University of Washington
Tommaso Patriarchi: University of Zürich

Nature Communications, 2024, vol. 15, issue 1, 1-20

Abstract: Abstract Nociceptin/orphanin-FQ (N/OFQ) is a recently appreciated critical opioid peptide with key regulatory functions in several central behavioral processes including motivation, stress, feeding, and sleep. The functional relevance of N/OFQ action in the mammalian brain remains unclear due to a lack of high-resolution approaches to detect this neuropeptide with appropriate spatial and temporal resolution. Here we develop and characterize NOPLight, a genetically encoded sensor that sensitively reports changes in endogenous N/OFQ release. We characterized the affinity, pharmacological profile, spectral properties, kinetics, ligand selectivity, and potential interaction with intracellular signal transducers of NOPLight in vitro. Its functionality was established in acute brain slices by exogeneous N/OFQ application and chemogenetic induction of endogenous N/OFQ release from PNOC neurons. In vivo studies with fibre photometry enabled direct recording of NOPLight binding to exogenous N/OFQ receptor ligands, as well as detection of endogenous N/OFQ release within the paranigral ventral tegmental area (pnVTA) during natural behaviors and chemogenetic activation of PNOC neurons. In summary, we show here that NOPLight can be used to detect N/OFQ opioid peptide signal dynamics in tissue and freely behaving animals.

Date: 2024
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DOI: 10.1038/s41467-024-49712-0

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