A genetically encoded sensor for in vivo imaging of orexin neuropeptides.
Creators
- Duffet, Loic1
- Kosar, Seher2
- Panniello, Mariangela3
- Viberti, Bianca4
- Bracey, Edward2
- Zych, Anna D.5
- Radoux-Mergault, Arthur6
- Zhou, Xuehan1
- Dernic, Jan1
- Ravotto, Luca1
- Tsai, Yuan-Chen1
- Figueiredo, Marta1
- Tyagarajan, Shiva K.1
- Weber, Bruno1
- Stoeber, Miriam6
- Gogolla, Nadine5
- Schmidt, Markus H.4
- Adamantidis, Antoine R.4
- Fellin, Tommaso3
- Burdakov, Denis2
- Patriarchi, Tommaso1
- 1. Institute of Pharmacology and Toxicology, University of Zurich, Zurich, Switzerland
- 2. Department of Health Sciences and Technology, ETH Zurich, Zurich, Switzerland
- 3. Optical Approaches to Brain Function Laboratory, Istituto Italiano di Tecnologia, Genova, Italy
- 4. Center for Experimental Neurology (ZEN), Department of Neurology, Inselspital University Hospital Bern, University of Bern, Bern, Switzerland
- 5. Circuits for Emotion Research Group, Max Planck Institute of Neurobiology, Martinsried, Germany
- 6. Department of Cell Physiology and Metabolism, University of Geneva, Geneva, Switzerland
Description
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.
Notes
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Additional details
Related works
- Is identical to
- 10.1038/s41592-021-01390-2 (DOI)
Funding
- OPTONEUROCHEM – Genetically encoded sensors for imaging neurochemical dynamics in vivo 891959
- European Commission
- InsularAnxiety – Insular cortical circuits controlling fear and anxiety 758448
- European Commission
- NEURO-PATTERNS – How neuronal activity patterns drive behavior: novel all-optical control and monitoring of brain neuronal networks with high spatiotemporal resolution 647725
- European Commission
- Mechanisms Underlying Subcellular Location Bias of Opioid Receptor Signaling PCEFP3_181282
- Swiss National Science Foundation
- Dissecting MCH and DA dynamics in vivo with novel genetically encoded sensors 310030_196455
- Swiss National Science Foundation
- Opto-Sleep – All-optical deconstruction of thalamic control of sleep-wake states. 725850
- European Commission
- DEEPER – DEEP BRAIN PHOTONIC TOOLS FOR CELL-TYPE SPECIFIC TARGETING OF NEURAL DISEASES 101016787
- European Commission