title: Noninvasive optical inhibition with a red-shifted microbial rhodopsin.
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.
authors.affiliation: 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.
authors.forename: Amy S
authors.initials: AS
authors.lastname: Chuong
authors.affiliation: 1] Department of Neurobiology, Yale School of Medicine, Yale University, New Haven, Connecticut, USA. [2].
authors.forename: Mitra L
authors.initials: ML
authors.lastname: Miri
authors.affiliation: 1] Neural Circuit Laboratories, Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland. [2] Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA. [3].
authors.forename: Volker
authors.initials: V
authors.lastname: Busskamp
authors.affiliation: 1] Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA. [2].
authors.forename: Gillian A C
authors.initials: GA
authors.lastname: Matthews
authors.affiliation: 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].
authors.forename: Leah C
authors.initials: LC
authors.lastname: Acker
authors.affiliation: McGovern Institute for Brain Research, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
authors.forename: Andreas T
authors.initials: AT
authors.lastname: Sørensen
authors.affiliation: McGovern Institute for Brain Research, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Young
authors.affiliation: 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.
authors.forename: Nathan C
authors.initials: NC
authors.lastname: Klapoetke
authors.affiliation: 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.
authors.forename: Mike A
authors.initials: MA
authors.lastname: Henninger
authors.affiliation: 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.
authors.forename: Suhasa B
authors.initials: SB
authors.lastname: Kodandaramaiah
authors.affiliation: 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.
authors.forename: Masaaki
authors.initials: M
authors.lastname: Ogawa
authors.affiliation: Department of Biomedical Engineering, Boston University, Boston, Massachusetts, USA.
authors.forename: Shreshtha B
authors.initials: SB
authors.lastname: Ramanlal
authors.affiliation: Media Lab, Department of Media Arts and Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
authors.forename: Rachel C
authors.initials: RC
authors.lastname: Bandler
authors.affiliation: Media Lab, Department of Media Arts and Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
authors.forename: Brian D
authors.initials: BD
authors.lastname: Allen
authors.affiliation: George W. Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, Georgia, USA.
authors.forename: Craig R
authors.initials: CR
authors.lastname: Forest
authors.affiliation: Department of Bioengineering, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Brian Y
authors.initials: BY
authors.lastname: Chow
authors.affiliation: Department of Biomedical Engineering, Boston University, Boston, Massachusetts, USA.
authors.forename: Xue
authors.initials: X
authors.lastname: Han
authors.affiliation: McGovern Institute for Brain Research, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
authors.forename: Yingxi
authors.initials: Y
authors.lastname: Lin
authors.affiliation: Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
authors.forename: Kay M
authors.initials: KM
authors.lastname: Tye
authors.affiliation: Neural Circuit Laboratories, Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland.
authors.forename: Botond
authors.initials: B
authors.lastname: Roska
authors.affiliation: 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.
authors.forename: Jessica A
authors.initials: JA
authors.lastname: Cardin
authors.affiliation: 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.
authors.forename: Edward S
authors.initials: ES
authors.lastname: Boyden
mesh_terms: D000818:Animals; D001923:Brain Chemistry / Q000502:physiology*; D019617:Halobacterium salinarum / Q000502:physiology*; D025602:Halorhodopsins / Q000502:physiology*; D051379:Mice; D008969:Molecular Sequence Data; D009433:Neural Inhibition / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D062308:Optogenetics / Q000379:methods*; D012160:Retina / Q000502:physiology
chemical_list: D025602:Halorhodopsins