An Orthogonal Near-Infrared Optical Switch for Wireless Neuromodulation in Freely Behaving Mice

Area of Science:

• Neuroscience
• Biotechnology
• Optogenetics

Background:

• Neuronal activity modulation is crucial for neuroscience research.
• Current methods like visible light optogenetics are invasive, while near-infrared (NIR) methods risk photothermal damage.
• A need exists for non-invasive, safe, and controllable neuromodulation techniques.

Purpose of the Study:

• To introduce a novel Dual-NIR Switch for transcranial, tether-free neuronal modulation in freely moving mice.
• To enable on-demand initiation and termination of neuronal activity using two distinct NIR wavelengths.
• To overcome limitations of existing neuromodulation technologies, particularly photothermal effects.

Main Methods:

• Utilized orthogonal dichromatic upconversion nanoparticles activated by 980 nm and 808 nm NIR light.
• Employed these nanoparticles to control the step-function opsin SOUL, activating with blue light and inactivating with green light.
• Administered sequential transcranial NIR illumination to freely moving mice for initiating and terminating neuronal activation.

Main Results:

• Demonstrated successful on-demand initiation and termination of neuronal activity using the Dual-NIR Switch.
• Achieved tunable control over behavioral paradigms in mice, with modulation durations ranging from seconds to subhours.
• Confirmed the elimination of sustained NIR illumination, mitigating photothermal concerns.

Conclusions:

• The Dual-NIR Switch provides a non-invasive, tether-free, and duration-tunable method for neuromodulation.
• This technology offers precise control over neuronal activity, applicable to basic neuroscience and potential therapeutic interventions.
• The system effectively addresses safety concerns associated with sustained NIR light exposure in optogenetics.