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Related Concept Videos

Channel Rhodopsins01:11

Channel Rhodopsins

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Most organisms use photoreceptors to sense and respond to light. Examples of photoreceptors include bacteriorhodopsins and bacteriophytochromes in some bacteria, phytochromes in plants, and rhodopsins in the photoreceptor cells of the vertebral retina. The light-sensitive property of these receptors is because of the bound chromophores, such as bilin in the phytochromes and retinal in the rhodopsins.
Rhodopsins belong to the family of cell surface proteins called G-protein coupled receptors,...
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Imaging Membrane Potential with Two Types of Genetically Encoded Fluorescent Voltage Sensors
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Sensitivity optimization of a rhodopsin-based fluorescent voltage indicator.

Ahmed S Abdelfattah1, Jihong Zheng2, Amrita Singh1

  • 1Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA, USA.

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|April 4, 2023
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Researchers developed Voltron2, a new voltage indicator with significantly improved sensitivity for optical imaging of brain activity. This advancement offers deeper insights into neural function in living animals.

Keywords:
biosensorsfluorescence imagingfluorescent proteinsgenetically encoded indicatorsvoltage imaging

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Area of Science:

  • Neuroscience
  • Biotechnology
  • Molecular Biology

Background:

  • Optical imaging of cellular transmembrane voltages is crucial for understanding brain function.
  • Existing voltage indicators have limitations in sensitivity and resolution.

Purpose of the Study:

  • To develop a more sensitive Ace2 opsin-based voltage indicator.
  • To improve the ability to optically image neural activity in vivo.

Main Methods:

  • Introduced a point mutation to enhance Ace2 opsin sensitivity.
  • Developed and validated the Voltron2 voltage indicator.
  • Performed in vitro and in vivo comparisons with existing indicators.
  • Utilized Voltron2 to investigate interneuron synchronization.

Main Results:

  • Voltron2 exhibits 65% higher sensitivity to single action potentials (APs) and 3-fold higher sensitivity to subthreshold potentials than Voltron.
  • Voltron2 maintains sub-millisecond kinetics and photostability.
  • Demonstrated superior sensitivity of Voltron2 in various species and conditions.
  • Successfully applied Voltron2 to study hippocampal interneuron synchronization.

Conclusions:

  • A generalizable mutation significantly enhances Ace2 rhodopsin-based voltage sensors.
  • Voltron2 represents a substantial improvement in voltage reporting capability for neuroscience research.
  • This new indicator facilitates deeper understanding of neural dynamics in behaving animals.