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 and Takayuki Yamashita ()
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Takanori Matsubara: Nagoya University
Takayuki Yanagida: Nara Institute of Science and Technology
Noriaki Kawaguchi: Nara Institute of Science and Technology
Takashi Nakano: Nara Institute of Science and Technology
Junichiro Yoshimoto: Nara Institute of Science and Technology
Maiko Sezaki: Kumamoto University
Hitoshi Takizawa: Kumamoto University
Satoshi P. Tsunoda: Nagoya Institute of Technology
Shin-ichiro Horigane: Nagoya University
Shuhei Ueda: Nagoya University
Sayaka Takemoto-Kimura: Nagoya University
Hideki Kandori: Nagoya Institute of Technology
Akihiro Yamanaka: Nagoya University
Takayuki Yamashita: Nagoya University

Nature Communications, 2021, vol. 12, issue 1, 1-12

Abstract: 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 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.

Date: 2021
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DOI: 10.1038/s41467-021-24717-1

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