期刊
NATURE METHODS
卷 19, 期 2, 页码 231-+出版社
NATURE PORTFOLIO
DOI: 10.1038/s41592-021-01390-2
关键词
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资金
- European Research Council (ERC) under the European Union [891959]
- University of Zurich
- Swiss National Science Foundation [310030_196455, PCEFP3_181282]
- Forschungskredit Candoc
- ETH Zurich
- ERC2017-STG [758448]
- ERC-2016-CoG [725850]
- University of Bern and Inselspital University Hospital
- ERC-2014-CoG [647725]
- National Institutes of Health Brain Initiative [U19 NS107464]
- H2020-ICT [101016787]
- Swiss National Science Foundation (SNF) [310030_196455, PCEFP3_181282] Funding Source: Swiss National Science Foundation (SNF)
- European Research Council (ERC) [647725, 891959, 758448, 725850] Funding Source: European Research Council (ERC)
This study developed a genetically encoded orexin sensor called OxLight1, which enables sensitive and direct optical detection of orexin neuropeptides in living animals with high spatiotemporal resolution. The sensor was used in mouse experiments to show that orexin release is associated with behaviors such as running, stress, and sleep-to-wake transitions.
Orexins (also called hypocretins) are hypothalamic neuropeptides that carry out essential functions in the central nervous system; however, little is known about their release and range of action in vivo owing to the limited resolution of current detection technologies. Here we developed a genetically encoded orexin sensor (OxLight1) based on the engineering of circularly permutated green fluorescent protein into the human type-2 orexin receptor. In mice OxLight1 detects optogenetically evoked release of endogenous orexins in vivo with high sensitivity. Photometry recordings of OxLight1 in mice show rapid orexin release associated with spontaneous running behavior, acute stress and sleep-to-wake transitions in different brain areas. Moreover, two-photon imaging of OxLight1 reveals orexin release in layer 2/3 of the mouse somatosensory cortex during emergence from anesthesia. Thus, OxLight1 enables sensitive and direct optical detection of orexin neuropeptides with high spatiotemporal resolution in living animals. OxLight1 is a genetically encoded sensor for the orexin neuropeptides. It has been applied in fiber photometry recordings and two-photon imaging in mice during a variety of behaviors.
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