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. Neuron, May 2020.


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…