Noninvasive optical inhibition with a red-shifted microbial rhodopsin

Mitra L Miri(McGovern Institute for Brain Research), Volker Busskamp(Yale University), Andrew J. Young(Friedrich Miescher Institute), Masaaki Ogawa(Massachusetts Institute of Technology), Shreshtha B Ramanlal(McGovern Institute for Brain Research), Craig R. Forest(McGovern Institute for Brain Research), Brian Y. Chow(McGovern Institute for Brain Research), Xue Han(McGovern Institute for Brain Research), Yingxi Lin(McGovern Institute for Brain Research), Botond Roska(McGovern Institute for Brain Research), Jessica A. Cardin(Massachusetts Institute of Technology), Amy S. Chuong(Boston University), Leah Acker(Massachusetts Institute of Technology), Henninger, Michael Alan(Massachusetts Institute of Technology), Suhasa B. Kodandaramaiah(Georgia Institute of Technology), Rachel C. Bandler(University of Pennsylvania), Brian D. Allen(Boston University), Edward S. Boyden(McGovern Institute for Brain Research), Sorensen, Andreas Toft(Massachusetts Institute of Technology), Nathan C Klapoetke(Friedrich Miescher Institute), Gillian A. Matthews(Yale University), Kay M. Tye(McGovern Institute for Brain Research)
DSpace@MIT (Massachusetts Institute of Technology)
February 1, 2014
Cited by 582Open Access
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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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