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

Author

Listed:
  • Xiaodong Tian

    (University of Virginia
    University of Virginia)

  • Yiyu Zhang

    (University of Virginia
    University of Virginia)

  • Xinyu Li

    (University of Virginia
    University of Virginia
    Inner Mongolia University)

  • Ying Xiong

    (University of Virginia
    University of Virginia)

  • Tianchen Wu

    (University of Virginia
    University of Virginia)

  • Hui-Wang Ai

    (University of Virginia
    University of Virginia
    University of Virginia)

Abstract

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 (Ca2+) 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.

Suggested Citation

  • Xiaodong Tian & Yiyu Zhang & Xinyu Li & Ying Xiong & Tianchen Wu & Hui-Wang Ai, 2022. "A luciferase prosubstrate and a red bioluminescent calcium indicator for imaging neuronal activity in mice," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-31673-x
    DOI: 10.1038/s41467-022-31673-x
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    References listed on IDEAS

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    1. Kenta Saito & Y-F Chang & Kazuki Horikawa & Noriyuki Hatsugai & Yuriko Higuchi & Mitsuru Hashida & Yu Yoshida & Tomoki Matsuda & Yoshiyuki Arai & Takeharu Nagai, 2012. "Luminescent proteins for high-speed single-cell and whole-body imaging," Nature Communications, Nature, vol. 3(1), pages 1-9, January.
    2. Kazushi Suzuki & Taichi Kimura & Hajime Shinoda & Guirong Bai & Matthew J. Daniels & Yoshiyuki Arai & Masahiro Nakano & Takeharu Nagai, 2016. "Five colour variants of bright luminescent protein for real-time multicolour bioimaging," Nature Communications, Nature, vol. 7(1), pages 1-10, December.
    3. Jie Yang & Derrick Cumberbatch & Samuel Centanni & Shu-qun Shi & Danny Winder & Donna Webb & Carl Hirschie Johnson, 2016. "Coupling optogenetic stimulation with NanoLuc-based luminescence (BRET) Ca++ sensing," Nature Communications, Nature, vol. 7(1), pages 1-10, December.
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