Language

English

Publication Date

9-1-2022

Journal

Cell

DOI

10.1016/j.cell.2022.07.013

PMID

35985322

PMCID

PMC9563101

PubMedCentral® Posted Date

10-14-2022

PubMedCentral® Full Text Version

Author MSS

Abstract

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.

In Brief

Engineering of a fast, sensitive, bright and photostable genetically encoded voltage indicator optimized for two-photon microscopy enables deep-tissue optical recording of rapid voltage dynamics over tens of minutes.

Keywords

Animals, Interneurons, Mice, Microscopy, Neurons, Photons, Wakefulness

Published Open-Access

yes

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