Noninvasive optical inhibition with a red-shifted microbial rhodopsin

Amy S Chuong, Mitra L Miri, Volker Busskamp, Gillian A C Matthews, Leah C Acker, Andreas T Sørensen, Andrew Young, Nathan C Klapoetke, Mike A Henninger, Suhasa B Kodandaramaiah, Masaaki Ogawa, Shreshtha B Ramanlal, Rachel C Bandler, Brian D Allen, Craig R Forest, Brian Y Chow, Xue Han, Yingxi Lin, Kay M Tye, Botond RoskaJessica A Cardin, Edward S Boyden

281 Citations (Scopus)

Abstract

Optogenetic inhibition of the electrical activity of neurons enables the causal assessment of their contributions to brain functions. Red light penetrates deeper into tissue than other visible wavelengths. We present a red-shifted cruxhalorhodopsin, Jaws, derived from Haloarcula (Halobacterium) salinarum (strain Shark) and engineered to result in red light-induced photocurrents three times those of earlier silencers. Jaws exhibits robust inhibition of sensory-evoked neural activity in the cortex and results in strong light responses when used in retinas of retinitis pigmentosa model mice. We also demonstrate that Jaws can noninvasively mediate transcranial optical inhibition of neurons deep in the brains of awake mice. The noninvasive optogenetic inhibition opened up by Jaws enables a variety of important neuroscience experiments and offers a powerful general-use chloride pump for basic and applied neuroscience.

Original languageEnglish
JournalNature Neuroscience
Volume17
Issue number8
Pages (from-to)1123-1129
Number of pages7
ISSN1097-6256
DOIs
Publication statusPublished - Aug 2014
Externally publishedYes

Keywords

  • Animals
  • Brain Chemistry
  • Halobacterium salinarum
  • Halorhodopsins
  • Mice
  • Molecular Sequence Data
  • Neural Inhibition
  • Neurons
  • Optogenetics
  • Retina
  • Journal Article
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Technical Report

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