Publication Date
10-12-2023
Journal
Nature Communications
DOI
10.1038/s41467-023-41975-3
PMID
37828037
PMCID
PMC10570354
PubMedCentral® Posted Date
10-12-2023
PubMedCentral® Full Text Version
Post-print
Published Open-Access
yes
Keywords
Mice, Animals, Microscopy, Neurons, Photons, Brain, Photic Stimulation, Optical imaging, Neuroscience, Sensors and probes, High-throughput screening
Abstract
Widefield imaging with genetically encoded voltage indicators (GEVIs) is a promising approach for understanding the role of large cortical networks in the neural coding of behavior. However, the limited performance of current GEVIs restricts their deployment for single-trial imaging of rapid neuronal voltage dynamics. Here, we developed a high-throughput platform to screen for GEVIs that combine fast kinetics with high brightness, sensitivity, and photostability under widefield one-photon illumination. Rounds of directed evolution produced JEDI-1P, a green-emitting fluorescent indicator with enhanced performance across all metrics. Next, we optimized a neonatal intracerebroventricular delivery method to achieve cost-effective and wide-spread JEDI-1P expression in mice. We also developed an approach to correct optical measurements from hemodynamic and motion artifacts effectively. Finally, we achieved stable brain-wide voltage imaging and successfully tracked gamma-frequency whisker and visual stimulations in awake mice in single trials, opening the door to investigating the role of high-frequency signals in brain computations.
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