Lin, DingchangLi, XiuyuanMoult, EricPark, PojeongTang, BenjaminShen, HaoGrimm, Jonathan B.Falco, NatalieJia, Bill Z.Baker, DavidLavis, Luke D.Cohen, Adam2023-07-272023-01-02Lin, Dingchang, Xiuyuan Li, Eric Moult, Pojeong Park, Benjamin Tang, Hao Shen, Jonathan B. Grimm et al. "Time-tagged ticker tapes for intracellular recordings." Nat Biotechnol 41, no. 5 (2023): 631-639. DOI: 10.1038/s41587-022-01524-71087-01561546-1696https://nrs.harvard.edu/URN-3:HUL.INSTREPOS:37376629AbstractA 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.en-USBiomedical EngineeringMolecular MedicineApplied Microbiology and BiotechnologyBioengineeringBiotechnologyJournal Article2023-07-2710.1038/s41587-022-01524-7