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Updated: Dec 22, 2025

In vivo Optogenetic Stimulation of the Rodent Central Nervous System
Published on: January 15, 2015
An Ultra-Sensitive Step-Function Opsin for Minimally Invasive Optogenetic Stimulation in Mice and Macaques
Xin Gong1, Diego Mendoza-Halliday2, Jonathan T Ting3
1Center for Integrative Imaging, Hefei National Laboratory for Physical Sciences at the Microscale, University of Science and Technology of China, Hefei, Anhui 230026, China; McGovern Institute for Brain Research, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Researchers developed a new ultra-sensitive optogenetic tool called SOUL. This minimally invasive method enables deep brain stimulation via transcranial light delivery in mice and macaques, offering new therapeutic possibilities.
Area of Science:
- Neuroscience
- Molecular Biology
- Biotechnology
Background:
- Optogenetics is crucial for neuronal manipulation but requires invasive fiber implantation.
- Existing methods face limitations in targeting deep brain regions and require surgical procedures.
Purpose of the Study:
- To engineer a novel, highly light-sensitive opsin for minimally invasive optogenetics.
- To demonstrate the efficacy of this new opsin in activating neurons and modulating brain activity non-invasively.
Main Methods:
- Development of a new step-function opsin with ultra-high light sensitivity (SOUL).
- Testing SOUL in deep brain regions of mice using transcranial optical stimulation.
- Evaluating SOUL's ability to modulate neuronal activity and behavior in knock-in mice.
- Assessing SOUL in non-human primates (macaques) for cortical stimulation outside the dura.
Main Results:
- SOUL successfully activated neurons in deep mouse brain regions via transcranial stimulation.
- SOUL elicited observable behavioral changes in knock-in mice.
- Neuronal spiking and oscillations were reversibly modulated in macaque cortex using external light delivery.
- Demonstrated feasibility of minimally invasive optogenetic control in both rodent and primate models.
Conclusions:
- The SOUL opsin provides a minimally invasive approach to optogenetics, overcoming the need for invasive optical fibers.
- This technique allows for targeted neuronal manipulation in deep brain structures and cortical areas.
- SOUL holds promise for advancing neuroscience research and developing new therapies for neurological disorders.

