基于光遗传学的在体高空间分辨率神经调控技术  

Advances on in vivo High-Spatial-Resolution Neural Manipulation Based on Optogenetics

作　　者：孔令杰[1,2] 靳程 金国藩 Kong Lingjie;Jin Cheng;Jin Guofan(State Key Laboratory of Precision Measurement Technology and Instruments,Department of Precision Instrument,Tsinghua University,Beijing 100084,China;IDG/Mc Govern Institute for Brain Research at Tsinghua,Beijing 100084,China)

机构地区：[1]清华大学精密仪器系精密测试技术与仪器国家重点实验室,北京100084 [2]清华-IDG/麦戈文脑科学研究院,北京100084

出　　处：《中国激光》2021年第15期310-321,共12页Chinese Journal of Lasers

基　　金：国家自然科学基金(61831014,61771287,32021002);清华大学自主科研计划(20193080076);清华大学Bio-Brian+X高端成像仪器开发种子基金。

摘　　要：相比传统电生理方法,基于光遗传学的神经调控技术具有低侵入性、可结合基因工程实现特定神经元选择性激发等优势,近年来在脑科学研究领域得到广泛应用。对基于光遗传学的神经调控方法进行了系统回顾,详细介绍了双光子光遗传技术及其在在体高空间分辨率神经调控方面的研究进展,包括串行螺旋扫描激发、串行扩展光斑扫描激发以及基于广义相衬和计算机生成全息图的并行激发技术等。此外,还讨论了目前双光子光遗传技术在激发精度及激发视场等方面存在的问题及解决方案,并指出将双光子成像与双光子光遗传结合的全光电生理技术可实现神经活动的同步观测与调控,进而极大地推动神经环路解析等神经科学研究。Significance Recently,neuroscience has attracted great attention around the world.To prompt the study of neuroscience,a lot of countries have launched brain projects,in which the development of advanced neural techniques is regarded as the driving force.Optical techniques own the advantages of being less-invasive and high spatial resolution,etc,promising for neural activity recording and manipulation.Compared to traditional electrode stimulation methods,optical stimulation based on optogenetics could selectively excite or inhibit specific neural ensembles,benefiting from the introduction of gene engineering.So far,a variety of opsins have been developed for the activation or inhibition of neural activity.On the other hand,to achieve selective manipulation at single-neuron resolution,the techniques for two-photon optogenetics are emerging.Here,we review various strategies for illumination in two-photon optogenetics.We summarize their technical principles,and discuss their advantages and disadvantages.Progress Illumination strategies in optogenetics can be classified as conventional illumination strategies based on single-photon absorption and high-spatial-resolution illumination strategies based on two-photon absorption.In the early days of optogenetics,the wide-field illumination strategy based on single-photon absorption was used to manipulate neurons with opsins.Due to the scattering and absorption of biological tissues,the power of illumination light decreases significantly with the increase of penetration depth in wide-field illumination strategy.For neuron manipulation in deep tissues,fiber-coupled illumination is performed,in which the excitation light is guided through the fiber to the targeted depth.However,specific manipulation of neural activity at single-neuron resolutions is not achieved in neither wide-field illumination nor fiber-coupled illumination,due to the fact that all neurons with opsins in the illumination region would be excited.For specific manipulation of neural activity at single-neuron

关 键 词：材料 光遗传学 光敏蛋白 双光子激发 计算全息算法 全光电生理系统 

分 类 号：R318.51[医药卫生—生物医学工程]