Upconversion Nanoparticles-Based Multiplex Protein Activation to Neuron Ablation for Locomotion Regulation

Area of Science:

• Neuroscience
• Biomedical Engineering
• Materials Science

Background:

• Optogenetic neuron ablation allows precise study of neuron function but is limited by shallow tissue penetration of visible light.
• Existing methods struggle with efficient ablation in deep tissues, hindering in vivo research and therapeutic applications.

Purpose of the Study:

• To develop a novel upconversion nanoparticle (UCNP)-based tool for efficient deep-tissue neuron ablation using near-infrared (NIR) light.
• To investigate the role of specific neurons in locomotion control through targeted ablation.
• To establish a platform for multiplexed cell ablation and neural circuit analysis.

Main Methods:

• Optimized UCNPs for enhanced blue and red light emission upon 808 nm irradiation.
• Engineered UCNPs to simultaneously activate a singlet oxygen generator and Chrimson for synergistic neuronal ablation.
• Utilized NIR light for deep tissue penetration and in vivo neuron elimination.

Main Results:

• Achieved over 300-fold enhancement in UCNP emissions, significantly boosting NIR light-induced neuronal ablation efficiency.
• Demonstrated that targeted neuron ablation via UCNPs severely inhibits reverse locomotion, confirming the neurons' role in motor control.
• Validated the feasibility of in vivo deep-tissue neuron elimination using the UCNP-based system.

Conclusions:

• The UCNP-based multiplex protein activation tool enables efficient, deep-tissue neuron photoablation with high spatiotemporal resolution.
• This technology provides a versatile platform for studying neural circuits underlying behavior and offers potential for remote therapeutic interventions.
• The developed system overcomes limitations of visible light optogenetics, paving the way for advanced neuroscience research and disease treatment.