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Nat Neurosci. 2014 Aug;17(8):1123-9. doi: 10.1038/nn.3752. Epub 2014 Jul 6.

Noninvasive optical inhibition with a red-shifted microbial rhodopsin.

Author information

1
1] Media Lab, Department of Media Arts and Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA. [2] McGovern Institute for Brain Research, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA. [3] Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
2
1] Department of Neurobiology, Yale School of Medicine, Yale University, New Haven, Connecticut, USA. [2].
3
1] Neural Circuit Laboratories, Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland. [2] Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA. [3].
4
1] Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA. [2].
5
1] Media Lab, Department of Media Arts and Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA. [2] McGovern Institute for Brain Research, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA. [3] Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA. [4].
6
McGovern Institute for Brain Research, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
7
1] Media Lab, Department of Media Arts and Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA. [2] McGovern Institute for Brain Research, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA. [3] Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA. [4] George W. Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, Georgia, USA.
8
Department of Biomedical Engineering, Boston University, Boston, Massachusetts, USA.
9
Media Lab, Department of Media Arts and Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
10
George W. Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, Georgia, USA.
11
Department of Bioengineering, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
12
Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
13
Neural Circuit Laboratories, Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland.
14
1] Department of Neurobiology, Yale School of Medicine, Yale University, New Haven, Connecticut, USA. [2] Kavli Institute for Neuroscience, Yale University, New Haven, Connecticut, USA.

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.

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PMID:
24997763
PMCID:
PMC4184214
DOI:
10.1038/nn.3752
[Indexed for MEDLINE]
Free PMC Article
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