Remote control of neural function by X-ray-induced scintillation.

Area of Science:

• Neuroscience
• Biomedical Engineering
• Materials Science

Background:

• Scintillators convert X-rays into visible light, offering potential for deep-tissue applications.
• Optogenetics allows precise control of genetically modified cells using light.
• Current optogenetic methods face limitations in tissue penetration depth.

Purpose of the Study:

• To investigate the use of inorganic scintillators for remote, deep-brain optogenetic control.
• To evaluate the efficacy and biocompatibility of Ce-doped Gd3(Al,Ga)5O12 (Ce:GAGG) microparticles for activating opsins.
• To demonstrate X-ray-mediated modulation of neural activity and behavior in vivo.

Main Methods:

• Injectable Ce:GAGG microparticles were developed and characterized.
• Activation of red-shifted excitatory (ChRmine) and inhibitory (GtACR1) opsins by Ce:GAGG luminescence was confirmed.
• Midbrain dopamine neurons in freely moving mice were targeted for X-ray irradiation.
• Behavioral changes, specifically place preference, were assessed following X-ray stimulation.

Main Results:

• Ce:GAGG microparticles successfully mediated X-ray-induced activation and inhibition of targeted neurons.
• Bidirectional modulation of place preference behavior was observed in mice.
• Ce:GAGG microparticles demonstrated non-cytotoxicity and biocompatibility for chronic implantation.
• Clinical-level pulsed X-ray doses were sufficient for behavioral changes without causing significant cellular damage.

Conclusions:

• Scintillator-mediated optogenetics offers a minimally invasive, wireless method for controlling cellular functions at any depth.
• This approach expands X-ray applications into functional studies in neuroscience and medicine.
• Ce:GAGG microparticles represent a promising tool for deep-brain optogenetic manipulation.