Sustained deep-tissue voltage recording using a fast indicator evolved for two-photon microscopy

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Liu, Zhuohe | Lu, Xiaoyu | Villette, Vincent | Gou, Yueyang | Colbert, Kevin | Lai, Shujuan | Guan, Sihui | Land, Michelle | Lee, Jihwan | Assefa, Tensae | Zollinger, Daniel | Korympidou, Maria | Vlasits, Anna | Pang, Michelle | Su, Sharon | Cai, Changjia | Froudarakis, Emmanouil | Zhou, Na | Patel, Saumil | Smith, Cameron | Ayon, Annick | Bizouard, Pierre | Bradley, Jonathan | Franke, Katrin | Clandinin, Thomas | Giovannucci, Andrea | Tolias, Andreas | Reimer, Jacob | Dieudonné, Stéphane | St-Pierre, François

Edité par CCSD ; Elsevier -

International audience. 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.

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