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Publication : A positively tuned voltage indicator for extended electrical recordings in the brain.

First Author  Evans SW Year  2023
Journal  Nat Methods Volume  20
Issue  7 Pages  1104-1113
PubMed ID  37429962 Mgi Jnum  J:359590
Mgi Id  MGI:7788573 Doi  10.1038/s41592-023-01913-z
Citation  Evans SW, et al. (2023) A positively tuned voltage indicator for extended electrical recordings in the brain. Nat Methods 20(7):1104-1113
abstractText  Genetically encoded voltage indicators (GEVIs) enable optical recording of electrical signals in the brain, providing subthreshold sensitivity and temporal resolution not possible with calcium indicators. However, one- and two-photon voltage imaging over prolonged periods with the same GEVI has not yet been demonstrated. Here, we report engineering of ASAP family GEVIs to enhance photostability by inversion of the fluorescence-voltage relationship. Two of the resulting GEVIs, ASAP4b and ASAP4e, respond to 100-mV depolarizations with >/=180% fluorescence increases, compared with the 50% fluorescence decrease of the parental ASAP3. With standard microscopy equipment, ASAP4e enables single-trial detection of spikes in mice over the course of minutes. Unlike GEVIs previously used for one-photon voltage recordings, ASAP4b and ASAP4e also perform well under two-photon illumination. By imaging voltage and calcium simultaneously, we show that ASAP4b and ASAP4e can identify place cells and detect voltage spikes with better temporal resolution than commonly used calcium indicators. Thus, ASAP4b and ASAP4e extend the capabilities of voltage imaging to standard one- and two-photon microscopes while improving the duration of voltage recordings.
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