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

Xin Gong; Diego Mendoza-Halliday; Jonathan T. Ting; Tobias Kaiser; Xuyun Sun; André M. Bastos; Ralf D. Wimmer; Baolin Guo; Qian Chen; Yang Zhou; Maxwell Pruner; Carolyn W.H. Wu; Demian Park; Karl Deisseroth; Boaz Barak; Edward S. Boyden; Earl K. Miller; Michael M. Halassa; Zhanyan Fu; Guoqiang Bi; Robert Desimone; Guoping Feng

doi:10.1016/j.neuron.2020.03.032

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

Xin Gong, Diego Mendoza-Halliday, Jonathan T. Ting, Tobias Kaiser, Xuyun Sun, André M. Bastos, Ralf D. Wimmer, Baolin Guo, Qian Chen, Yang Zhou, Maxwell Pruner, Carolyn W.H. Wu, Demian Park, Karl Deisseroth, Boaz Barak, Edward S. Boyden, Earl K. Miller, Michael M. Halassa, Zhanyan Fu, Guoqiang BiRobert Desimone^*, Guoping Feng^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

94 Scopus citations

Abstract

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.

Original language	English
Pages (from-to)	38-51.e8
Journal	Neuron
Volume	107
Issue number	1
DOIs	https://doi.org/10.1016/j.neuron.2020.03.032
State	Published - 8 Jul 2020
Externally published	Yes

Funding

Funders	Funder number
Broad Institute of MIT
Harvard
James and Patricia Poitras Center for Psychiatric Disorders Research
NIH/NINDS
Simons Center for the Social Brain
National Institutes of Health
National Institute of Mental Health	P50MH094271
National Institute of Neurological Disorders and Stroke	R01 NS113245
Massachusetts Institute of Technology
Harvard University
Broad Institute
China Scholarship Council

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Gong, X., Mendoza-Halliday, D., Ting, J. T., Kaiser, T., Sun, X., Bastos, A. M., Wimmer, R. D., Guo, B., Chen, Q., Zhou, Y., Pruner, M., Wu, C. W. H., Park, D., Deisseroth, K., Barak, B., Boyden, E. S., Miller, E. K., Halassa, M. M., Fu, Z., ... Feng, G. (2020). An Ultra-Sensitive Step-Function Opsin for Minimally Invasive Optogenetic Stimulation in Mice and Macaques. Neuron, 107(1), 38-51.e8. https://doi.org/10.1016/j.neuron.2020.03.032

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

abstract = "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.",

author = "Xin Gong and Diego Mendoza-Halliday and Ting, {Jonathan T.} and Tobias Kaiser and Xuyun Sun and Bastos, {Andr{\'e} M.} and Wimmer, {Ralf D.} and Baolin Guo and Qian Chen and Yang Zhou and Maxwell Pruner and Wu, {Carolyn W.H.} and Demian Park and Karl Deisseroth and Boaz Barak and Boyden, {Edward S.} and Miller, {Earl K.} and Halassa, {Michael M.} and Zhanyan Fu and Guoqiang Bi and Robert Desimone and Guoping Feng",

note = "Publisher Copyright: {\textcopyright} 2020 Elsevier Inc.",

year = "2020",

month = jul,

day = "8",

doi = "10.1016/j.neuron.2020.03.032",

language = "אנגלית",

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Gong, X, Mendoza-Halliday, D, Ting, JT, Kaiser, T, Sun, X, Bastos, AM, Wimmer, RD, Guo, B, Chen, Q, Zhou, Y, Pruner, M, Wu, CWH, Park, D, Deisseroth, K, Barak, B, Boyden, ES, Miller, EK, Halassa, MM, Fu, Z, Bi, G, Desimone, R & Feng, G 2020, 'An Ultra-Sensitive Step-Function Opsin for Minimally Invasive Optogenetic Stimulation in Mice and Macaques', Neuron, vol. 107, no. 1, pp. 38-51.e8. https://doi.org/10.1016/j.neuron.2020.03.032

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T1 - An Ultra-Sensitive Step-Function Opsin for Minimally Invasive Optogenetic Stimulation in Mice and Macaques

AU - Gong, Xin

AU - Mendoza-Halliday, Diego

AU - Ting, Jonathan T.

AU - Kaiser, Tobias

AU - Sun, Xuyun

AU - Bastos, André M.

AU - Wimmer, Ralf D.

AU - Guo, Baolin

AU - Chen, Qian

AU - Zhou, Yang

AU - Pruner, Maxwell

AU - Wu, Carolyn W.H.

AU - Park, Demian

AU - Deisseroth, Karl

AU - Barak, Boaz

AU - Boyden, Edward S.

AU - Miller, Earl K.

AU - Halassa, Michael M.

AU - Fu, Zhanyan

AU - Bi, Guoqiang

AU - Desimone, Robert

AU - Feng, Guoping

PY - 2020/7/8

Y1 - 2020/7/8

N2 - 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.

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

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