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bioRxiv · 10.1101/2021.12.06.471018

A luciferase prosubstrate and a red bioluminescent calcium indicator to image neuronal activity

Tian, X.·Zhang, Y.·Li, X.·Xiong, Y.·Wu, T.·Ai, H.
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Abstract

Genetically encoded fluorescent indicators have been broadly used to monitor neuronal activity in live animals, but invasive surgical procedures are required. This study presents a functional bioluminescence imaging (fBLI) method for recording the activity of neuronal ensembles in the brain in awake mice. We developed a luciferase prosubstrate activatable in vivo by nonspecific esterase to enhance the brain delivery of the luciferin. We further engineered a bright, bioluminescent indicator with robust responsiveness to calcium ions (Ca2+) and appreciable emission above 600 nm. Integration of these advantageous components enabled the imaging of Ca2+ dynamics in awake mice minimally invasively with excellent signal- to-background and subsecond temporal resolution. This study thus establishes a new paradigm for studying brain functions in health and disease.

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Tian, X., Zhang, Y., Li, X., Xiong, Y., Wu, T., Ai, H.. 2021-12-07. A luciferase prosubstrate and a red bioluminescent calcium indicator to image neuronal activity. https://doi.org/10.1101/2021.12.06.471018

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