TY - JOUR
T1 - Comparative Validation of Scintillator Materials for X-Ray-Mediated Neuronal Control in the Deep Brain
AU - Hildebrandt, Mercedes
AU - Koshimizu, Masanori
AU - Asada, Yasuki
AU - Fukumitsu, Kansai
AU - Okuma, Mahito
AU - Sang, Na
AU - Nakano, Takashi
AU - Kunikata, Toshiaki
AU - Okazaki, Kai
AU - Kawaguchi, Noriaki
AU - Yanagida, Takayuki
AU - Lian, Linyuan
AU - Zhang, Jianbing
AU - Yamashita, Takayuki
N1 - Publisher Copyright:
© 2024 by the authors.
PY - 2024/11
Y1 - 2024/11
N2 - When exposed to X-rays, scintillators emit visible luminescence. X-ray-mediated optogenetics employs scintillators for remotely activating light-sensitive proteins in biological tissue through X-ray irradiation. This approach offers advantages over traditional optogenetics, allowing for deeper tissue penetration and wireless control. Here, we assessed the short-term safety and efficacy of candidate scintillator materials for neuronal control. Our analyses revealed that lead-free halide scintillators, such as Cs3Cu2I5, exhibited significant cytotoxicity within 24 h and induced neuroinflammatory effects when injected into the mouse brain. In contrast, cerium-doped gadolinium aluminum gallium garnet (Ce:GAGG) nanoparticles showed no detectable cytotoxicity within the same period, and injection into the mouse brain did not lead to observable neuroinflammation over four weeks. Electrophysiological recordings in the cerebral cortex of awake mice showed that X-ray-induced radioluminescence from Ce:GAGG nanoparticles reliably activated 45% of the neuronal population surrounding the implanted particles, a significantly higher activation rate than europium-doped GAGG (Eu:GAGG) microparticles, which activated only 10% of neurons. Furthermore, we established the cell-type specificity of this technique by using Ce:GAGG nanoparticles to selectively stimulate midbrain dopamine neurons. This technique was applied to freely behaving mice, allowing for wireless modulation of place preference behavior mediated by midbrain dopamine neurons. These findings highlight the unique suitability of Ce:GAGG nanoparticles for X-ray-mediated optogenetics. The deep tissue penetration, short-term safety, wireless neuronal control, and cell-type specificity of this system offer exciting possibilities for diverse neuroscience applications and therapeutic interventions.
AB - When exposed to X-rays, scintillators emit visible luminescence. X-ray-mediated optogenetics employs scintillators for remotely activating light-sensitive proteins in biological tissue through X-ray irradiation. This approach offers advantages over traditional optogenetics, allowing for deeper tissue penetration and wireless control. Here, we assessed the short-term safety and efficacy of candidate scintillator materials for neuronal control. Our analyses revealed that lead-free halide scintillators, such as Cs3Cu2I5, exhibited significant cytotoxicity within 24 h and induced neuroinflammatory effects when injected into the mouse brain. In contrast, cerium-doped gadolinium aluminum gallium garnet (Ce:GAGG) nanoparticles showed no detectable cytotoxicity within the same period, and injection into the mouse brain did not lead to observable neuroinflammation over four weeks. Electrophysiological recordings in the cerebral cortex of awake mice showed that X-ray-induced radioluminescence from Ce:GAGG nanoparticles reliably activated 45% of the neuronal population surrounding the implanted particles, a significantly higher activation rate than europium-doped GAGG (Eu:GAGG) microparticles, which activated only 10% of neurons. Furthermore, we established the cell-type specificity of this technique by using Ce:GAGG nanoparticles to selectively stimulate midbrain dopamine neurons. This technique was applied to freely behaving mice, allowing for wireless modulation of place preference behavior mediated by midbrain dopamine neurons. These findings highlight the unique suitability of Ce:GAGG nanoparticles for X-ray-mediated optogenetics. The deep tissue penetration, short-term safety, wireless neuronal control, and cell-type specificity of this system offer exciting possibilities for diverse neuroscience applications and therapeutic interventions.
KW - deep brain stimulation
KW - dopamine
KW - electrophysiology
KW - nanoparticles
KW - optogenetics
KW - scintillator
KW - toxicity
KW - X-rays
UR - http://www.scopus.com/inward/record.url?scp=85208584107&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85208584107&partnerID=8YFLogxK
U2 - 10.3390/ijms252111365
DO - 10.3390/ijms252111365
M3 - Article
C2 - 39518918
AN - SCOPUS:85208584107
SN - 1661-6596
VL - 25
JO - International journal of molecular sciences
JF - International journal of molecular sciences
IS - 21
M1 - 11365
ER -