LSO:Ce Inorganic Scintillators Are Biocompatible With Neuronal and Circuit Function
LSO:Ce Inorganic Scintillators Are Biocompatible With Neuronal and Circuit Function
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DOI：
10.3389/fnsyn.2019.00024
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发表时间：
2019-09-03
影响因子：
3.7
通讯作者：
Dobrunz, Lynn E.
中科院分区：
文献类型：
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作者：
Bartley, Aundrea F.;Abiraman, Kavitha;Dobrunz, Lynn E.
光遗传学在神经科学中被广泛用于控制神经回路。然而，为了避免现有方法造成的身体损伤，需要非侵入性的脑内光线传递方法。一种潜在的策略可能是使用X射线激活放射发光粒子(RPL)，使大脑能够局部产生光。由无机闪烁体组成的RPLS可以发射不同波长的光，具体取决于其组成。掺CeO：Ce是一种无机闪烁体，能在X射线或紫外线(U)刺激下发出蓝光，可通过激活光门控阳离子通道视紫红质-2(ChR2)来控制神经回路。无机闪烁体本身是否会对神经元过程和突触功能产生负面影响尚不清楚，我们在这里用细胞、分子和电生理方法进行了研究。作为原理的证明，我们在全细胞记录谷氨酸能神经元表达ChR2的小鼠急性海马片CA1锥体细胞的过程中，对4微米LSO：Ce颗粒进行了紫外线刺激。我们观察到自发兴奋性突触后电流(SEPSCs)的频率和幅度增加，表明ChR2激活和神经元兴奋。重要的是，LSO：Ce颗粒不影响原代小鼠皮质神经元的存活，即使在暴露24小时后也是如此。在细胞外树突场电位记录中，在LSO：Ce微粒暴露期间，基础谷氨酸能传递的强度没有变化。然而，在高强度刺激下，纤维凌空的波幅略有降低。此外，在CA1锥体细胞的全细胞电压钳记录中，sEPSCs的频率略有下降，但电流幅度没有变化。自发抑制性突触后电流的幅度和频率没有变化。最后，成功地诱导了长时程增强(LTP)，这是一种突触修饰，被认为是学习和记忆的基础，也是突触完整性的稳健衡量标准，尽管幅度略有降低。综上所述，这些结果表明LSO：Ce颗粒是生物相容的，尽管对基线突触功能和长期突触可塑性的影响很小。重要的是，我们证明了LSO：Ce颗粒发出的光能够激活ChR2并改变突触功能。因此，LSO：Ce无机闪烁体作为光遗传学的一种新的光传输系统具有潜在的应用前景。
Optogenetics is widely used in neuroscience to control neural circuits. However, non-invasive methods for light delivery in brain are needed to avoid physical damage caused by current methods. One potential strategy could employ x-ray activation of radioluminescent particles (RPLs), enabling localized light generation within the brain. RPLs composed of inorganic scintillators can emit light at various wavelengths depending upon composition. Cerium doped lutetium oxyorthosilicate (LSO:Ce), an inorganic scintillator that emits blue light in response to x-ray or ultraviolet (U\/) stimulation, could potentially be used to control neural circuits through activation of channelrhodopsin-2 (ChR2), a light-gated cation channel. Whether inorganic scintillators themselves negatively impact neuronal processes and synaptic function is unknown, and was investigated here using cellular, molecular, and electrophysiological approaches. As proof of principle, we applied UV stimulation to 4 mu m LSO:Ce particles during whole-cell recording of CA1 pyramidal cells in acute hippocampal slices from mice that expressed ChR2 in glutamatergic neurons. We observed an increase in frequency and amplitude of spontaneous excitatory postsynaptic currents (sEPSCs), indicating activation of ChR2 and excitation of neurons. Importantly, LSO:Ce particles did not affect survival of primary mouse cortical neurons, even after 24 h of exposure. In extracellular dendritic field potential recordings, no change in the strength of basal glutamatergic transmission was observed during exposure to LSO:Ce microparticles. However, the amplitude of the fiber volley was slightly reduced with high stimulation. Additionally, there was a slight decrease in the frequency of sEPSCs in whole-cell voltage-clamp recordings from CA1 pyramidal cells, with no change in current amplitudes. The amplitude and frequency of spontaneous inhibitory postsynaptic currents were unchanged. Finally, long term potentiation (LTP), a synaptic modification believed to underlie learning and memory and a robust measure of synaptic integrity, was successfully induced, although the magnitude was slightly reduced. Together, these results show LSO:Ce particles are biocompatible even though there are modest effects on baseline synaptic function and long-term synaptic plasticity. Importantly, we show that light emitted from LSO:Ce particles is able to activate ChR2 and modify synaptic function. Therefore, LSO:Ce inorganic scintillators are potentially viable for use as a new light delivery system for optogenetics.