Sustained deep-tissue voltage recording using a fast indicator evolved for two-photon microscopy.
Cell
; 185(18): 3408-3425.e29, 2022 09 01.
Article
in En
| MEDLINE
| ID: mdl-35985322
Genetically encoded voltage indicators are emerging tools for monitoring voltage dynamics with cell-type specificity. However, current indicators enable a narrow range of applications due to poor performance under two-photon microscopy, a method of choice for deep-tissue recording. To improve indicators, we developed a multiparameter high-throughput platform to optimize voltage indicators for two-photon microscopy. Using this system, we identified JEDI-2P, an indicator that is faster, brighter, and more sensitive and photostable than its predecessors. We demonstrate that JEDI-2P can report light-evoked responses in axonal termini of Drosophila interneurons and the dendrites and somata of amacrine cells of isolated mouse retina. JEDI-2P can also optically record the voltage dynamics of individual cortical neurons in awake behaving mice for more than 30 min using both resonant-scanning and ULoVE random-access microscopy. Finally, ULoVE recording of JEDI-2P can robustly detect spikes at depths exceeding 400 µm and report voltage correlations in pairs of neurons.
Key words
Full text:
1
Database:
MEDLINE
Main subject:
Microscopy
/
Neurons
Limits:
Animals
Language:
En
Journal:
Cell
Year:
2022
Type:
Article
Affiliation country:
United States