Protocol for whole-tissue immunolabeling, optical clearing, and lightsheet imaging of c-Fos protein expression in unsectioned mouse brains

Summary: The c-Fos protein has been broadly utilized as a marker of neuronal activity, and conventional immunohistochemistry to determine its expression relies on tissue sections. Here, we present a protocol to visualize the endogenous c-Fos protein in intact, unsectioned mouse brains responding to...

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Main Authors: Koukou Fu, Jing Yang
Format: Article
Language:English
Published: Elsevier 2025-06-01
Series:STAR Protocols
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Online Access:http://www.sciencedirect.com/science/article/pii/S2666166725002746
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author Koukou Fu
Jing Yang
author_facet Koukou Fu
Jing Yang
author_sort Koukou Fu
collection DOAJ
description Summary: The c-Fos protein has been broadly utilized as a marker of neuronal activity, and conventional immunohistochemistry to determine its expression relies on tissue sections. Here, we present a protocol to visualize the endogenous c-Fos protein in intact, unsectioned mouse brains responding to specific stimuli based on the immunolabeling-enabled three-dimensional imaging of solvent-cleared organs (iDISCO) method. We describe steps for tissue harvesting, fixation, decolorization, and permeabilization followed by whole-tissue anti-c-Fos immunolabeling. We then detail procedures for tissue embedding and optical clearing for imaging by lightsheet microscopy.For complete details on the use and execution of this protocol, please refer to Chen et al.1 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.
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publishDate 2025-06-01
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spelling doaj-art-4d9b6321c2b348b9b4ecc1cd2440bd642025-08-20T03:18:23ZengElsevierSTAR Protocols2666-16672025-06-016210386810.1016/j.xpro.2025.103868Protocol for whole-tissue immunolabeling, optical clearing, and lightsheet imaging of c-Fos protein expression in unsectioned mouse brainsKoukou Fu0Jing Yang1State Key Laboratory of Membrane Biology, School of Life Sciences, Center for Life Sciences, IDG/McGovern Institute for Brain Research, Peking University Third Hospital Cancer Center, Peking University, Beijing 100871, ChinaState Key Laboratory of Membrane Biology, School of Life Sciences, Center for Life Sciences, IDG/McGovern Institute for Brain Research, Peking University Third Hospital Cancer Center, Peking University, Beijing 100871, China; Peking Union Medical College Hospital, Beijing 100730, China; Corresponding authorSummary: The c-Fos protein has been broadly utilized as a marker of neuronal activity, and conventional immunohistochemistry to determine its expression relies on tissue sections. Here, we present a protocol to visualize the endogenous c-Fos protein in intact, unsectioned mouse brains responding to specific stimuli based on the immunolabeling-enabled three-dimensional imaging of solvent-cleared organs (iDISCO) method. We describe steps for tissue harvesting, fixation, decolorization, and permeabilization followed by whole-tissue anti-c-Fos immunolabeling. We then detail procedures for tissue embedding and optical clearing for imaging by lightsheet microscopy.For complete details on the use and execution of this protocol, please refer to Chen et al.1 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.http://www.sciencedirect.com/science/article/pii/S2666166725002746MicroscopyNeuroscienceBiotechnology and bioengineering
spellingShingle Koukou Fu
Jing Yang
Protocol for whole-tissue immunolabeling, optical clearing, and lightsheet imaging of c-Fos protein expression in unsectioned mouse brains
STAR Protocols
Microscopy
Neuroscience
Biotechnology and bioengineering
title Protocol for whole-tissue immunolabeling, optical clearing, and lightsheet imaging of c-Fos protein expression in unsectioned mouse brains
title_full Protocol for whole-tissue immunolabeling, optical clearing, and lightsheet imaging of c-Fos protein expression in unsectioned mouse brains
title_fullStr Protocol for whole-tissue immunolabeling, optical clearing, and lightsheet imaging of c-Fos protein expression in unsectioned mouse brains
title_full_unstemmed Protocol for whole-tissue immunolabeling, optical clearing, and lightsheet imaging of c-Fos protein expression in unsectioned mouse brains
title_short Protocol for whole-tissue immunolabeling, optical clearing, and lightsheet imaging of c-Fos protein expression in unsectioned mouse brains
title_sort protocol for whole tissue immunolabeling optical clearing and lightsheet imaging of c fos protein expression in unsectioned mouse brains
topic Microscopy
Neuroscience
Biotechnology and bioengineering
url http://www.sciencedirect.com/science/article/pii/S2666166725002746
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AT jingyang protocolforwholetissueimmunolabelingopticalclearingandlightsheetimagingofcfosproteinexpressioninunsectionedmousebrains