Liu, Z., Lu, X., Villette, V., Gou, Y., Colbert, K.L., Lai, S., Guan, S., Land, M.A., Lee, J., Assefa, T., Zollinger, D.R., Korympidou, M.M., Vlasits, A.L., Pang, M.M., Su, S., Cai, C., Froudarakis, E., Zhou, N., Patel, S.S., Smith, C.L., Ayon, A., Bizouard, P., Bradley, J., Franke, K., Clandinin, T.R., Giovannucci, A., Tolias, A.S., Reimer, J., Dieudonné, S., St-Pierre, F. (2022). Sustained deep-tissue voltage recording using a fast indicator evolved for two-photon microscopy.  Cell 185(18): 3408--3425.e29.

FBrf0254411

Research paper

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.

PMC9563101 (PMC) (EuropePMC)