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 journalArticlepeer-review

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 languageEnglish
Pages (from-to)38-51.e8
JournalNeuron
Volume107
Issue number1
DOIs
StatePublished - 8 Jul 2020
Externally publishedYes

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