物理化学学报

所属专题: 神经界面

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基于上转换纳米粒子的低损伤神经界面技术

邹亮1,2, 田慧慧1   

  1. 1 中国科学院纳米科学卓越创新中心, 国家纳米科学中心, 北京 100190;
    2 中国科学院大学, 北京 100049
  • 收稿日期:2020-03-19 修回日期:2020-04-21 录用日期:2020-04-22 发布日期:2020-04-27
  • 通讯作者: 田慧慧 E-mail:tianhh@nanoctr.cn
  • 基金资助:
    国家自然科学基金项目(21790393,61971150)和中国科学院先导B项目(XDB32030100)资助

Upconversion Nanoparticles-Mediated Optogenetics for Minimally Invasive Neural Interface

Liang Zou1,2, Huihui Tian1   

  1. 1 CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing 100190, P. R. China;
    2 University of Chinese Academy of Sciences, Beijing 100049, P. R. China
  • Received:2020-03-19 Revised:2020-04-21 Accepted:2020-04-22 Published:2020-04-27
  • Supported by:
    The project was supported by the National Natural Science Foundation of China (21790393, 61971150) and the Special Fund for Strategic Pilot Technology of Chinese Academy of Sciences (XDB32030100).

摘要: 光遗传技术能够实现对特定类型神经元的高时间分辨调控。过去几年,光遗传技术在神经环路的结构与功能研究中得到了广泛应用,并且在神经疾病治疗领域具有良好的应用前景。目前光遗传常用光敏蛋白的激发波长位于可见光波段。可见光的组织穿透性差,很难通过组织外照射来调控动物大脑深部的神经元电活动,因此极大地限制了光遗传技术的应用。上转换纳米粒子可以将组织穿透性好的近红外光转换成可见光激活光敏蛋白,从而可以实现可见光的远程、低损伤递送。近几年来,基于上转换纳米粒子的光遗传技术得到了迅速发展。本文将总结基于上转换纳米粒子的光遗传技术的研究现状及技术瓶颈,并且结合柔性神经电极技术的发展,对构建可以同时调控与检测活体大脑电活动的低损伤、双向神经界面进行了展望。

关键词: 上转换纳米粒子, 转换效率, 光遗传, 神经调控, 基因技术

Abstract: ptogenetics is a neuromodulation technology that combines light control technology with genetic technology, thus allowing the selective activation and inhibition of the electrical activity in specific types of neurons with millisecond time resolution. Over the past several years, optogenetics has become a powerful tool for understanding the organization and functions of neural circuits, and it holds great promise to treat neurological disorders. To date, the excitation wavelengths of commonly employed opsins in optogenetics are located in the visible spectrum. This poses a serious limitation for neural activity regulation because the intense absorption and scattering of visible light by tissues lead to the loss of excitation light energy and also cause tissue heating. To regulate the activity of neurons in deep brain regions, it is necessary to implant optical fibers or optoelectronic devices into target brain areas, which however can induce severe tissue damage. Non-or minimally-invasive remote control technologies that can manipulate neural activity have been highly desirable in neuroscience research. Upconversion nanoparticles (UCNPs) can emit light with a short wavelength and high frequency upon excitation by light with a long wavelength and low frequency. Therefore, UCNPs can convert low-frequency near-infrared (NIR) light into high-frequency visible light for the activation of light-sensitive proteins, thus indirectly realizing the NIR optogenetic system. Because NIR light has a large tissue penetration depth, UCNP-mediated optogenetics has attracted significant interest for deep-tissue neuromodulation. However, in UCNP-mediated in vivo optogenetic experiments, as the up-conversion efficiency of UCNPs is low, it is generally necessary to apply high-power NIR light to obtain up-converted fluorescence with energy high enough to activate a photosensitive protein. High-power NIR light can cause thermal damage to tissues, which seriously restricts the applications of UCNPs in optogenetic technology. Therefore, the exploration of strategies to increase the up-conversion efficiency, fluorescence intensity, and biocompatibility of UCNPs is of great significance to their wide applications in optogenetic systems. This review summarizes recent developments and challenges in UCNP-mediated optogenetics for deep-brain neuromodulation. We firstly discuss the correspondence between the parameters of UCNPs and employed opsins in optogenetic experiments, which mainly include excitation wavelengths, emission wavelengths, and luminescent lifetimes. Thereafter, we introduce the methods to enhance the conversion efficiency of UCNPs, including optimizing the structure of UCNPs and modifying the organic dyes in UCNPs. In addition, we also discuss the future opportunities in combining UCNP-mediated optogenetics with flexible microelectrode technology for the long-term detection and regulation of neural activity in the case of minimal injury.

Key words: Upconversion nanoparticle, Conversion efficiency, Optogenetics, Neural regulation, Genetic technology

MSC2000: 

  • O646