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

Takanori Matsubara; Yanagida Takayuki; 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

doi:10.1038/s41467-021-24717-1

NeuroscienceNature CommunicationsJul 22, 2021

Peer-reviewed journal article

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

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

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), could 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 were non-cytotoxic and biocompatible, allowing for chronic implantation. Pulsed X-ray irradiation at a clinical dose level was sufficient to elicit behavioral changes without reducing the number of radiosensitive cells in the brain and bone marrow. Thus, scintillator-mediated optogenetics enables less 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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