Department of Neuroscience II, Research Institute of Environmental Medicine, Nagoya University, Nagoya, Japan.
Department of Neural Regulation, Graduate School of Medicine, Nagoya University, Nagoya, Japan.
Nat Commun. 2021 Jul 22;12(1):4478. doi: 10.1038/s41467-021-24717-1.
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 Gd(Al,Ga)O (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.
闪烁体受到 X 射线照射时会发出可见光。由于 X 射线的组织穿透能力无限，闪烁体的应用可以实现在大脑的任何深度对神经功能进行远程光遗传学控制。在这里，我们表明，一种黄色发射无机闪烁体，Ce 掺杂的 Gd(Al,Ga)O(Ce:GAGG)，可以分别有效地激活红移兴奋性和抑制性光感受器 ChRmine 和 GtACR1。使用可注射的 Ce:GAGG 微米颗粒，我们通过 X 射线照射成功地激活和抑制了自由活动小鼠的中脑多巴胺神经元，产生了对位置偏好行为的双向调制。Ce:GAGG 微米颗粒是非细胞毒性和生物相容性的，允许进行慢性植入。临床剂量水平的脉冲 X 射线照射足以引起行为变化，而不会减少大脑和骨髓中对辐射敏感的细胞数量。因此，闪烁体介导的光遗传学使在活体动物的任何组织深度都可以进行微创、无线的细胞功能控制，将 X 射线的应用扩展到生物学和医学的功能研究。
