Wireless Optogenetic Modulation of Cortical Neurons Enabled by Radioluminescent Nanoparticles

Area of Science:

• Neuroscience
• Biomedical Engineering
• Materials Science

Background:

• Optogenetics offers precise neural circuit control but requires invasive fiber-optic implants.
• Current methods face challenges in delivering light to deep brain structures non-invasively.
• Developing wireless, minimally invasive stimulation techniques is crucial for clinical translation.

Purpose of the Study:

• To develop a novel, minimally invasive method for wireless deep brain stimulation.
• To utilize X-ray-activated radioluminescent nanoparticles for optogenetic activation.
• To demonstrate transcranial optogenetic control of cortical neurons.

Main Methods:

• Synthesized and characterized Gd2(WO4)3:Eu nanoparticles for X-ray to visible light conversion.
• Administered nanoparticles and applied external X-ray irradiation.
• Utilized red-shifted channelrhodopsin ReaChR expressed in cortical neurons.
• Performed transcranial stimulation and recorded neural responses.

Main Results:

• Gd2(WO4)3:Eu nanoparticles efficiently downconverted X-ray energy to visible photons (~610 nm).
• X-ray-activated nanoparticles successfully stimulated cortical neurons expressing ReaChR (~590-630 nm).
• Demonstrated transcranial optogenetic activation, enabling minimally invasive wireless deep brain stimulation.

Conclusions:

• X-ray-activated radioluminescent nanoparticles provide a viable platform for minimally invasive optogenetics.
• This approach facilitates wireless deep brain stimulation, overcoming the limitations of fiber-optic delivery.
• The findings pave the way for practical clinical applications of optogenetics in deep brain regions.