TY - JOUR
T1 - Remote control of neural function by X-ray-induced scintillation
AU - Matsubara, Takanori
AU - Yanagida, Takayuki
AU - Kawaguchi, Noriaki
AU - Nakano, Takashi
AU - Yoshimoto, Junichiro
AU - Sezaki, Maiko
AU - Takizawa, Hitoshi
AU - Tsunoda, Satoshi P.
AU - Horigane, Shin ichiro
AU - Ueda, Shuhei
AU - Takemoto-Kimura, Sayaka
AU - Kandori, Hideki
AU - Yamanaka, Akihiro
AU - Yamashita, Takayuki
N1 - Publisher Copyright:
© 2021, The Author(s).
PY - 2021/12/1
Y1 - 2021/12/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85111151982&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85111151982&partnerID=8YFLogxK
U2 - 10.1038/s41467-021-24717-1
DO - 10.1038/s41467-021-24717-1
M3 - Article
C2 - 34294698
AN - SCOPUS:85111151982
SN - 2041-1723
VL - 12
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 4478
ER -