基于DNA条形码技术的高通量介观联接组学  

DNA Barcode-based High-throughput Mesoscale Connectomics

作　　者：胡鹏凯 黄龙文 HU Peng-Kai;HUANG Long-Wen(State Key Laboratory of Brain and Cognitive Science,Institute of Biophysics,Chinese Academy of Sciences,Beijing 100101,China;College of Life Sciences,University of Chinese Academy of Sciences,Beijing 100049,China)

机构地区：[1]中国科学院生物物理研究所,脑与认知科学国家重点实验室,北京100101 [2]中国科学院大学生命科学学院,北京100049

出　　处：《生物化学与生物物理进展》2024年第10期2369-2378,共10页Progress In Biochemistry and Biophysics

基　　金：科技部科技创新2030-“脑科学与类脑研究”重大项目(2022ZD0206900);国家自然科学基金(32271143)资助。

摘　　要：联接组学作为研究不同脑区、不同神经元之间突触联接模式的一个重要神经科学研究领域,是理解神经计算,揭示情感、学习、认知等复杂功能的关键之一。其中微米级的介观联接组学以其独有的优势成为了目前在啮齿类动物等的神经系统研究中应用最为广泛的技术,且在非人灵长类动物的脑科学研究中也有着重要的应用前景。传统的介观联接组学测量技术通常采用荧光标记和光学成像的原理,对神经环路进行顺行或逆行示踪。为了实现单细胞精度的示踪成像以绘制更精细的联接图谱,人们发明了稀疏标记神经元的方法,但在单个动物的示踪通量、数据的多组学跨模态整合等方面仍面临着挑战。近十年来,基于DNA条形码的高通量介观联接组测量技术正快速发展,与传统的介观联接组学测量技术相比具有高通量、低成本以及多组学分析的优势。本文根据示踪原理及所用病毒感染模式的不同介绍了几种较成熟的基于DNA条形码的介观联接组学代表性技术,并从技术原理、技术应用以及技术的优缺点等方面进行总结。最后,总结了基于DNA条形码的高通量介观联接组测量技术领域的发展现状,并提出了一些未来的研究方向。Connectomics,a research field in neuroscience studying the synaptic connectivity patterns between neurons across different brain regions,is crucial for understanding neural computations underlying complex functions such as emotion,learning,and cognition.Specifically,micrometer-resolution mesoscale connectomics has become the most widely used technology in rodent neuroscience due to its unique advantages,and it also has the potential to transform brain research in non-human primates.Traditional mesoscale connectome techniques typically use fluorescence labeling and optical imaging to perform anterograde or retrograde tracing of neural circuits.To achieve single-cell resolution,methods for sparse labeling of neurons have been developed.However,it remains challenging to trace neurons in high throughput in individual animals and integrate multi-omics data across modalities.In the past decade,high-throughput mesoscale connectome technologies based on DNA barcoding have made significant progress.These technologies have provided novel tools to map single cell connectome,with higher throughput,lower cost,and multi-omics compatibility.Here we review several mature mesoscale connectome technologies based on DNA barcoding,discussing their principles,applications,advantages and disadvantages.We also propose future directions for barcoding-based connectomics.

关 键 词：DNA条形码 介观联接组 脑联接图谱 

分 类 号：Q189[生物学—神经生物学] Q-331[生物学—普通生物学]