An Ultra-Sensitive Step-Function Opsin for Minimally Invasive Optogenetic Stimulation in Mice and Macaques

© 2020 Elsevier Inc. Optogenetics is among the most widely employed techniques to manipulate neuronal activity. However, a major drawback is the need for invasive implantation of optical fibers. To develop a minimally invasive optogenetic method that overcomes this challenge, we engineered a new ste...

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Main Authors: Gong, Xin, Mendoza-Halliday, Diego, Ting, Jonathan T, Kaiser, Tobias, Sun, Xuyun, Bastos, André M, Wimmer, Ralf D, Guo, Baolin, Chen, Qian, Zhou, Yang, Pruner, Maxwell, Wu, Carolyn W-H, Park, Demian, Deisseroth, Karl, Barak, Boaz, Boyden, Edward S, Miller, Earl K, Halassa, Michael M, Fu, Zhanyan, Bi, Guoqiang, Desimone, Robert, Feng, Guoping
Format: Article
Language:English
Published: Elsevier BV 2021
Online Access:https://hdl.handle.net/1721.1/136482
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author Gong, Xin
Mendoza-Halliday, Diego
Ting, Jonathan T
Kaiser, Tobias
Sun, Xuyun
Bastos, André M
Wimmer, Ralf D
Guo, Baolin
Chen, Qian
Zhou, Yang
Pruner, Maxwell
Wu, Carolyn W-H
Park, Demian
Deisseroth, Karl
Barak, Boaz
Boyden, Edward S
Miller, Earl K
Halassa, Michael M
Fu, Zhanyan
Bi, Guoqiang
Desimone, Robert
Feng, Guoping
author_facet Gong, Xin
Mendoza-Halliday, Diego
Ting, Jonathan T
Kaiser, Tobias
Sun, Xuyun
Bastos, André M
Wimmer, Ralf D
Guo, Baolin
Chen, Qian
Zhou, Yang
Pruner, Maxwell
Wu, Carolyn W-H
Park, Demian
Deisseroth, Karl
Barak, Boaz
Boyden, Edward S
Miller, Earl K
Halassa, Michael M
Fu, Zhanyan
Bi, Guoqiang
Desimone, Robert
Feng, Guoping
author_sort Gong, Xin
collection MIT
description © 2020 Elsevier Inc. Optogenetics is among the most widely employed techniques to manipulate neuronal activity. However, a major drawback is the need for invasive implantation of optical fibers. To develop a minimally invasive optogenetic method that overcomes this challenge, we engineered a new step-function opsin with ultra-high light sensitivity (SOUL). We show that SOUL can activate neurons located in deep mouse brain regions via transcranial optical stimulation and elicit behavioral changes in SOUL knock-in mice. Moreover, SOUL can be used to modulate neuronal spiking and induce oscillations reversibly in macaque cortex via optical stimulation from outside the dura. By enabling external light delivery, our new opsin offers a minimally invasive tool for manipulating neuronal activity in rodent and primate models with fewer limitations on the depth and size of target brain regions and may further facilitate the development of minimally invasive optogenetic tools for the treatment of neurological disorders.
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spelling mit-1721.1/1364822021-10-28T04:54:12Z An Ultra-Sensitive Step-Function Opsin for Minimally Invasive Optogenetic Stimulation in Mice and Macaques Gong, Xin Mendoza-Halliday, Diego Ting, Jonathan T Kaiser, Tobias Sun, Xuyun Bastos, André M Wimmer, Ralf D Guo, Baolin Chen, Qian Zhou, Yang Pruner, Maxwell Wu, Carolyn W-H Park, Demian Deisseroth, Karl Barak, Boaz Boyden, Edward S Miller, Earl K Halassa, Michael M Fu, Zhanyan Bi, Guoqiang Desimone, Robert Feng, Guoping © 2020 Elsevier Inc. Optogenetics is among the most widely employed techniques to manipulate neuronal activity. However, a major drawback is the need for invasive implantation of optical fibers. To develop a minimally invasive optogenetic method that overcomes this challenge, we engineered a new step-function opsin with ultra-high light sensitivity (SOUL). We show that SOUL can activate neurons located in deep mouse brain regions via transcranial optical stimulation and elicit behavioral changes in SOUL knock-in mice. Moreover, SOUL can be used to modulate neuronal spiking and induce oscillations reversibly in macaque cortex via optical stimulation from outside the dura. By enabling external light delivery, our new opsin offers a minimally invasive tool for manipulating neuronal activity in rodent and primate models with fewer limitations on the depth and size of target brain regions and may further facilitate the development of minimally invasive optogenetic tools for the treatment of neurological disorders. 2021-10-27T20:35:36Z 2021-10-27T20:35:36Z 2020 2021-07-14T17:50:28Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/136482 en 10.1016/J.NEURON.2020.03.032 Neuron Creative Commons Attribution-Noncommercial-Share Alike http://creativecommons.org/licenses/by-nc-sa/4.0/ application/pdf Elsevier BV PMC
spellingShingle Gong, Xin
Mendoza-Halliday, Diego
Ting, Jonathan T
Kaiser, Tobias
Sun, Xuyun
Bastos, André M
Wimmer, Ralf D
Guo, Baolin
Chen, Qian
Zhou, Yang
Pruner, Maxwell
Wu, Carolyn W-H
Park, Demian
Deisseroth, Karl
Barak, Boaz
Boyden, Edward S
Miller, Earl K
Halassa, Michael M
Fu, Zhanyan
Bi, Guoqiang
Desimone, Robert
Feng, Guoping
An Ultra-Sensitive Step-Function Opsin for Minimally Invasive Optogenetic Stimulation in Mice and Macaques
title An Ultra-Sensitive Step-Function Opsin for Minimally Invasive Optogenetic Stimulation in Mice and Macaques
title_full An Ultra-Sensitive Step-Function Opsin for Minimally Invasive Optogenetic Stimulation in Mice and Macaques
title_fullStr An Ultra-Sensitive Step-Function Opsin for Minimally Invasive Optogenetic Stimulation in Mice and Macaques
title_full_unstemmed An Ultra-Sensitive Step-Function Opsin for Minimally Invasive Optogenetic Stimulation in Mice and Macaques
title_short An Ultra-Sensitive Step-Function Opsin for Minimally Invasive Optogenetic Stimulation in Mice and Macaques
title_sort ultra sensitive step function opsin for minimally invasive optogenetic stimulation in mice and macaques
url https://hdl.handle.net/1721.1/136482
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