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Related Experiment Video

Updated: May 6, 2026

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

Zhuohe Liu1, Xiaoyu Lu2, Vincent Villette3

  • 1Department of Electrical and Computer Engineering, Rice University, Houston, TX 77005, USA.

Cell
|August 19, 2022
PubMed
Summary
This summary is machine-generated.

We developed JEDI-2P, a new genetically encoded voltage indicator that significantly improves performance for two-photon microscopy, enabling deeper and more precise neural activity monitoring in vivo.

Keywords:
GEVIJEDI-2Pfly visiongenetically encoded voltage indicatorhigh-throughput screeningpairwise voltage correlationsrandom-access microscopystarburst amacrine cellstwo-photon fluorescence microscopyvoltage imaging

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Area of Science:

  • Neuroscience
  • Biotechnology
  • Microscopy

Background:

  • Genetically encoded voltage indicators (GEVIs) are crucial for cell-type-specific voltage dynamics monitoring.
  • Current GEVIs exhibit limitations in performance, particularly under two-photon microscopy, hindering deep-tissue neural recordings.

Purpose of the Study:

  • To optimize GEVIs for enhanced performance with two-photon microscopy.
  • To develop a novel GEVIs, JEDI-2P, with improved speed, brightness, sensitivity, and photostability.

Main Methods:

  • Development of a multiparameter high-throughput platform for GEVIs optimization.
  • Application of the platform to identify and characterize JEDI-2P.
  • In vivo and ex vivo validation of JEDI-2P in Drosophila, mouse retina, and awake behaving mice.

Main Results:

  • JEDI-2P demonstrates superior speed, brightness, sensitivity, and photostability compared to existing indicators.
  • Successfully reported light-evoked responses in Drosophila interneurons and mouse retinal amacrine cells.
  • Enabled long-term optical recording of individual cortical neurons in awake mice using resonant-scanning and ULoVE microscopy.
  • ULoVE recording with JEDI-2P detected spikes at depths >400 μm and revealed neuronal voltage correlations.

Conclusions:

  • JEDI-2P represents a significant advancement in GEVIs for two-photon microscopy.
  • This indicator facilitates high-resolution voltage imaging in deep neural circuits.
  • JEDI-2P opens new avenues for studying neural circuit function in vivo.