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Time-tagged ticker tapes for intracellular recordings

Dingchang Lin, Xiuyuan (Ted) Li, Pojeong Park, Benjamin Tang, Hao Shen, Jonathan B. Grimm, Natalie Falco, David Baker, View ORCID ProfileLuke D. Lavis, View ORCID ProfileAdam E. Cohen
doi: https://doi.org/10.1101/2021.10.13.463862
Dingchang Lin
1Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138
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Xiuyuan (Ted) Li
1Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138
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Pojeong Park
1Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138
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Benjamin Tang
1Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138
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Hao Shen
2University of Washington, Molecular Engineering and Sciences, Seattle, WA 98195
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Jonathan B. Grimm
3Janelia Research Campus, Howard Hughes Medical Institute, 19700 Helix Drive, Ashburn, VA 20147
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Natalie Falco
3Janelia Research Campus, Howard Hughes Medical Institute, 19700 Helix Drive, Ashburn, VA 20147
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David Baker
2University of Washington, Molecular Engineering and Sciences, Seattle, WA 98195
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Luke D. Lavis
3Janelia Research Campus, Howard Hughes Medical Institute, 19700 Helix Drive, Ashburn, VA 20147
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  • ORCID record for Luke D. Lavis
Adam E. Cohen
1Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138
4Department of Physics, Harvard University, Cambridge, MA 02138
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  • ORCID record for Adam E. Cohen
  • For correspondence: cohen@chemistry.harvard.edu
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Abstract

A core taken in a tree today can reveal climate events from centuries past. Here we adapt this idea to record histories of neural activation. We engineered slowly growing intracellular protein fibers which can incorporate diverse fluorescent marks during growth to store linear ticker tape-like histories. An embedded HaloTag reporter incorporated user-supplied HaloTag-ligand dyes, leading to colored stripes whose boundaries mapped fiber growth to wall-clock time. A co-expressed eGFP tag driven by the cFos immediate early gene promoter recorded the history of neural activity. High-resolution multispectral imaging on fixed samples read the cellular histories. We demonstrated recordings of cFos activation in ensembles of cultured neurons with a single-cell absolute accuracy of approximately 39 min over a 12-hour interval. Protein-based ticker tapes have the potential to achieve massively parallel single-cell recordings of multiple physiological modalities.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • ↵† dingchang{at}g.harvard.edu

  • ↵§ cohen{at}chemistry.harvard.edu

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 4.0 International license.
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Posted October 14, 2021.
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Time-tagged ticker tapes for intracellular recordings
Dingchang Lin, Xiuyuan (Ted) Li, Pojeong Park, Benjamin Tang, Hao Shen, Jonathan B. Grimm, Natalie Falco, David Baker, Luke D. Lavis, Adam E. Cohen
bioRxiv 2021.10.13.463862; doi: https://doi.org/10.1101/2021.10.13.463862
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Time-tagged ticker tapes for intracellular recordings
Dingchang Lin, Xiuyuan (Ted) Li, Pojeong Park, Benjamin Tang, Hao Shen, Jonathan B. Grimm, Natalie Falco, David Baker, Luke D. Lavis, Adam E. Cohen
bioRxiv 2021.10.13.463862; doi: https://doi.org/10.1101/2021.10.13.463862

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