Airy-beam holographic sonogenetics for advancing neuromodulation precision and flexibility

Area of Science:

• Neuroscience
• Biomedical Engineering
• Medical Physics

Background:

• Understanding brain function and treating neurological diseases requires precise, non-invasive methods to control specific neuron groups.
• Current neuromodulation techniques often involve invasive procedures, limiting their application and flexibility.

Purpose of the Study:

• To introduce Airy-beam holographic sonogenetics (AhSonogenetics) as an implant-free, cell type-specific, spatially precise, and flexible neuromodulation technique.
• To demonstrate the capability of AhSonogenetics in modulating neuronal populations in freely moving mice and its potential therapeutic applications.

Main Methods:

• Development of wearable ultrasound devices using 3D-printed Airy-beam holographic metasurfaces.
• Utilizing genetically engineered neurons expressing ultrasound-sensitive ion channels for targeted manipulation.
• Employing ultrasound frequency tuning to dynamically steer Airy beams for precise spatial control.
• Integration with in vivo calcium recording via fiber photometry for simultaneous monitoring.

Main Results:

• AhSonogenetics enabled precise, cell type-specific neuromodulation without implants in freely moving mice.
• The system demonstrated flexible stimulation of specific striatal subregions, including independent left or right striatal modulation.
• Bilateral stimulation using double foci was achieved, and motor deficits in Parkinson's disease mouse models were alleviated.

Conclusions:

• AhSonogenetics provides a powerful, non-invasive tool for investigating neural circuits with high spatial and cell-type specificity.
• This technology offers a flexible and adaptable approach for neuromodulation, overcoming limitations of current methods.
• AhSonogenetics holds significant promise for developing novel interventions for neurological disorders like Parkinson's disease.