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

Scintillators exhibit visible luminescence, called scintillation, when irradiated with X-rays. Given that X-rays penetrate through biological tissues, X-ray-induced scintillation would enable remote optogenetic control of neural functions at any depths in the brain. Here we show that a yellow-emitting inorganic scintillator, Ce-doped Gd3(Al,Ga)5O12 (Ce:GAGG), can effectively activate red-shifted excitatory and inhibitory opsins. Using these scintillator-opsin combinations, we successfully activated and inhibited midbrain dopamine neurons of freely moving mice by X-ray irradiation, producing bi-directional modulation of place preference behavior. The Ce:GAGG crystal was biocompatible and could be implanted for a long period without progressive neuroinflammatory responses. Neither brain injury nor behavioral dysfunction was acutely induced by radiation during the behavioral tests. Thus, X-ray-induced scintillation allows wireless control of cellular functions in living animals, expanding X-ray applications to functional studies of biology and medicine.