A luciferase prosubstrate and a red bioluminescent calcium indicator for imaging neuronal activity in mice

Although fluorescent indicators have been broadly utilized for monitoring bioactivities, fluorescence imaging, when applied to mammals, is limited to superficial targets or requires invasive surgical procedures. Thus, there is emerging interest in developing bioluminescent indicators for noninvasive...

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Bibliographic Details
Published in:Nature communications 2022-07, Vol.13 (1), p.3967-13, Article 3967
Main Authors: Tian, Xiaodong, Zhang, Yiyu, Li, Xinyu, Xiong, Ying, Wu, Tianchen, Ai, Hui-Wang
Format: Article
Language:English
Subjects:
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Animals
Bioluminescence
Brain
Calcium
Calcium imaging
Calcium ions
Engineers
Esterase
Fluorescence
Fluorescent indicators
Humanities and Social Sciences
Integration
Ions
Luciferases
Luminescent Measurements - methods
Mammals
Medical imaging
Mice
multidisciplinary
Neuroimaging
Neurons
Optical Imaging
Photons
Science
Science (multidisciplinary)
Temporal resolution
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Summary:Although fluorescent indicators have been broadly utilized for monitoring bioactivities, fluorescence imaging, when applied to mammals, is limited to superficial targets or requires invasive surgical procedures. Thus, there is emerging interest in developing bioluminescent indicators for noninvasive mammalian imaging. Bioluminescence imaging (BLI) of neuronal activity is highly desired but hindered by insufficient photons needed to digitalize fast brain activities. In this work, we develop a luciferase prosubstrate deliverable at an increased dose and activated in vivo by nonspecific esterase. We further engineer a bright, bioluminescent indicator with robust responsiveness to calcium ions (Ca 2+ ) and appreciable emission above 600 nm. Integration of these advantageous components enables the imaging of the activity of neuronal ensembles in awake mice minimally invasively with excellent signal-to-background and subsecond temporal resolution. This study thus establishes a paradigm for studying brain function in health and disease. Bioluminescence imaging of neuronal activity is desired. Here the authors report a luciferase prosubstrate activatable in vivo by nonspecific esterase and engineer a bioluminescent indicator with responsiveness to calcium ions: integration of these components enabled imaging of neuronal activity in mice.
ISSN:2041-1723
2041-1723
DOI:10.1038/s41467-022-31673-x