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

Matsubara, Takanori; Yanagida, Takayuki; Kawaguchi, Noriaki; Nakano, Takashi; Yoshimoto, Junichiro; Sezaki, Maiko; Takizawa, Hitoshi; Tsunoda, Satoshi P et al. · Nat Commun · 2021

basic_science · Level V

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Abstract

Scintillators emit visible luminescence when irradiated with X-rays. Given the unlimited tissue penetration of X-rays, the employment of scintillators could enable remote optogenetic control of neural functions at any depth of the brain. Here we show that a yellow-emitting inorganic scintillator, Ce-doped Gd<sub>3</sub>(Al,Ga)<sub>5</sub>O<sub>12</sub> (Ce:GAGG), can effectively activate red-shifted excitatory and inhibitory opsins, ChRmine and GtACR1, respectively. Using injectable Ce:GAGG microparticles, we successfully activated and inhibited midbrain dopamine neurons in freely moving mice by X-ray irradiation, producing bidirectional modulation of place preference behavior. Ce:GAGG microparticles are non-cytotoxic and biocompatible, allowing for chronic implantation. Pulsed X-ray irradiation at a clinical dose level is sufficient to elicit behavioral changes without reducing the number of radiosensitive cells in the brain and bone marrow. Thus, scintillator-mediated optogenetics enables minimally invasive, wireless control of cellular functions at any tissue depth in living animals, expanding X-ray applications to functional studies of biology and medicine.

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