Sustained deep-tissue voltage recording using a fast indicator evolved for two-photon microscopy
Liu, Zhuohe; Lu, Xiaoyu; Villette, Vincent; Gou, Yueyang; Colbert, Kevin L.; More... Lai, Shujuan; Guan, Sihui; Land, Michelle A.; Lee, Jihwan; Assefa, Tensae; Zollinger, Daniel R.; Korympidou, Maria M.; Vlasits, Anna L.; Pang, Michelle M.; Su, Sharon; Cai, Changjia; Froudarakis, Emmanouil; Zhou, Na; Patel, Saumil S.; Smith, Cameron L.; Ayon, Annick; Bizouard, Pierre; Bradley, Jonathan; Franke, Katrin; Clandinin, Thomas R.; Giovannucci, Andrea; Tolias, Andreas S.; Reimer, Jacob; Dieudonné, Stéphane; St-Pierre, François Less...
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.