Department of Chemistry, Institutes of Brain Science, State Key Laboratory of Molecular Engineering of Polymers, State Key Laboratory of Medical Neurobiology, MOE Frontiers Center for Brain Science, Fudan University, Shanghai, 200433, P. R. China.
Department of Hand Surgery, Huashan Hospital, Priority Among Priorities of Shanghai Municipal Clinical Medicine Center, National Clinical Research Center for Aging and Medicine, Department of Hand and Upper Extremity Surgery, Jing'an District Central Hospital of Shanghai, Shanghai, 200040, China.
Nat Commun. 2021 Sep 27;12(1):5662. doi: 10.1038/s41467-021-25993-7.
Using multi-color visible lights for independent optogenetic manipulation of multiple neuronal populations offers the ability for sophisticated brain functions and behavior dissection. To mitigate invasive fiber insertion, infrared light excitable upconversion nanoparticles (UCNPs) with deep tissue penetration have been implemented in optogenetics. However, due to the chromatic crosstalk induced by the multiple emission peaks, conventional UCNPs or their mixture cannot independently activate multiple targeted neuronal populations. Here, we report NIR multi-color optogenetics by the well-designed trichromatic UCNPs with excitation-specific luminescence. The blue, green and red color emissions can be separately tuned by switching excitation wavelength to match respective spectral profiles of optogenetic proteins ChR2, C1V1 and ChrimsonR, which enables selective activation of three distinct neuronal populations. Such stimulation with tunable intensity can not only activate distinct neuronal populations selectively, but also achieve transcranial selective modulation of the motion behavior of awake-mice, which opens up a possibility of multi-color upconversion optogenetics.
使用多色可见光对多个神经元群体进行独立的光遗传学操控，为深入剖析大脑功能和行为提供了可能。为了减轻纤维插入的侵入性，具有深组织穿透能力的红外光可激发上转换纳米粒子（UCNP）已被应用于光遗传学。然而，由于多发射峰引起的色串扰，传统的 UCNP 或其混合物不能独立地激活多个靶向神经元群体。在这里，我们通过设计合理的三基色 UCNP 报告了近红外多色光遗传学，该 UCNP 具有激发特异性发光。通过切换激发波长来分别调整蓝、绿和红光发射，可以与光遗传学蛋白 ChR2、C1V1 和 ChrimsonR 的相应光谱特性匹配，从而能够选择性地激活三个不同的神经元群体。这种可调强度的刺激不仅可以选择性地激活不同的神经元群体，还可以实现对清醒小鼠运动行为的经颅选择性调制，为多色上转换光遗传学开辟了可能性。
