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Fluorescence lifetime enables high-resolution analysis of neuromodulator dynamics across time and animals

View ORCID ProfilePingchuan Ma, Peter Chen, Elizabeth Tilden, Samarth Aggarwal, Anna Oldenborg, View ORCID ProfileYao Chen
doi: https://doi.org/10.1101/2022.09.28.510014
Pingchuan Ma
1Department of Neuroscience, Washington University in St. Louis, St. Louis, MO 63110
2Ph.D. Program in Neuroscience, Washington University in St. Louis
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Peter Chen
1Department of Neuroscience, Washington University in St. Louis, St. Louis, MO 63110
3Master’s Program in Biomedical Engineering, Washington University in St. Louis
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Elizabeth Tilden
1Department of Neuroscience, Washington University in St. Louis, St. Louis, MO 63110
2Ph.D. Program in Neuroscience, Washington University in St. Louis
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Samarth Aggarwal
1Department of Neuroscience, Washington University in St. Louis, St. Louis, MO 63110
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Anna Oldenborg
1Department of Neuroscience, Washington University in St. Louis, St. Louis, MO 63110
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Yao Chen
1Department of Neuroscience, Washington University in St. Louis, St. Louis, MO 63110
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  • For correspondence: yaochen@wustl.edu
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ABSTRACT

The dynamics of neuromodulators are essential for their functions. Optical sensors have transformed the study of neuromodulators because they capture neuromodulator dynamics with high spatial and temporal resolution. However, fluorescence intensity-based sensors are restricted to measure acute changes within one animal over a short period because intensity varies with sensor expression level and excitation light fluctuation. In contrast, fluorescence lifetime is impervious to sensor expression level or excitation light power, allowing comparison between individuals and across long periods. Here, we discover fluorescence lifetime response in multiple intensity-based neuromodulator sensors. Using the acetylcholine sensor GRABACh3.0 to investigate the power of lifetime measurement, we find that fluorescence lifetime correlates with animal behavior states accurately despite varying excitation power or changes in sensor expression level across weeks and animals. Thus, fluorescence lifetime of neuromodulator sensors enables comparison of neuromodulator dynamics at high resolution between animals and for chronic time scales.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • Updated with additional analysis and text revision.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted March 17, 2023.
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Fluorescence lifetime enables high-resolution analysis of neuromodulator dynamics across time and animals
Pingchuan Ma, Peter Chen, Elizabeth Tilden, Samarth Aggarwal, Anna Oldenborg, Yao Chen
bioRxiv 2022.09.28.510014; doi: https://doi.org/10.1101/2022.09.28.510014
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Fluorescence lifetime enables high-resolution analysis of neuromodulator dynamics across time and animals
Pingchuan Ma, Peter Chen, Elizabeth Tilden, Samarth Aggarwal, Anna Oldenborg, Yao Chen
bioRxiv 2022.09.28.510014; doi: https://doi.org/10.1101/2022.09.28.510014

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