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

Takanori Matsubara, Takayuki Yanagida, Noriaki Kawaguchi, Takashi Nakano, Junichiro Yoshimoto, Maiko Sezaki, Hitoshi Takizawa, Satoshi P. Tsunoda, Shin ichiro Horigane, Shuhei Ueda, Sayaka Takemoto-Kimura, Hideki Kandori, Akihiro Yamanaka, Takayuki Yamashita

Research output: Contribution to journalArticlepeer-review

24 Citations (Scopus)


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 Gd3(Al,Ga)5O12 (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.

Original languageEnglish
Article number4478
JournalNature communications
Issue number1
Publication statusPublished - 01-12-2021

All Science Journal Classification (ASJC) codes

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)


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