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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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Related Experiment Video

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In vivo Optogenetic Stimulation of the Rodent Central Nervous System
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Machine learning-guided channelrhodopsin engineering enables minimally invasive optogenetics.

Claire N Bedbrook1, Kevin K Yang2, J Elliott Robinson1

  • 1Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA.

Nature Methods
|October 16, 2019
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Summary

Researchers engineered novel channelrhodopsins (ChRs) for less invasive brain circuit studies. One variant, ChRger2, enables transcranial optogenetics, activating neurons with light without implants.

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Area of Science:

  • Neuroscience
  • Molecular Biology
  • Biotechnology

Background:

  • Optogenetics enables neuronal circuit interrogation using light-activated ion channels.
  • Current optogenetic tools in mammals necessitate invasive surgery for gene delivery and fiber implantation.
  • Existing channelrhodopsins (ChRs) have limitations in current strength and light sensitivity for widespread application.

Purpose of the Study:

  • To engineer novel light-gated channelrhodopsins (ChRs) for minimally invasive neuronal circuit interrogation.
  • To develop ChRs enabling optogenetics without intracranial implants, facilitating broader applications.
  • To design high-performance ChRs with enhanced photocurrent and light sensitivity.

Main Methods:

  • Leveraged existing literature on ChR variants to train statistical models.
  • Employed Gaussian process models trained on 102 functionally characterized ChRs.
  • Designed and characterized novel ChR variants (ChRger1-3) for high performance.

Main Results:

  • Engineered high-photocurrent ChRs with improved light sensitivity.
  • Identified three ChR variants (ChRger1-3) enabling systemic transgene delivery for optogenetic activation.
  • Demonstrated that ChRger2 enables light-induced neuronal excitation without fiber-optic implantation, achieving transcranial optogenetics.

Conclusions:

  • Novel ChRs (ChRger1-3) significantly advance optogenetic capabilities for neuronal circuit interrogation.
  • ChRger2 represents a breakthrough, enabling non-invasive transcranial optogenetics via systemic delivery.
  • These engineered ChRs pave the way for more accessible and expansive optogenetic research in the mammalian brain.