Continuous subcellular resolution three-dimensional imaging on intact macaque brain

• 作者: Can Zhou Xiaoquan Yang Shihao Wu Qiuyuan Zhong Ting Luo Anan Li Guangcai Liu Qingtao Sun Pan Luo Lei Deng Hong Ni Chaozhen Tan Jing Yuan Qingming Luo Xintian Hu Xiangning Li Hui Gong
• 来源期刊: 科学通报（英文版）
• 年，卷（期）: 2022,（1）
• 所属期刊栏目: Life Sciences
• 页码范围: 85-96
• 页数: 12页
• 语种: 英文

摘要

To decipher the organizational logic of complex brain circuits,it is important to chart long-distance path-ways while preserving micron-level accuracy of local network.However,mapping the neuronal projec-tions with individual-axon resolution in the large and complex primate brain is still challenging.Herein,we describe a highly efficient pipeline for three-dimensional mapping of the entire macaque brain with subcellular resolution.The pipeline includes a novel poly-N-acryloyl glycinamide (PNAGA)-based embedding method for long-term structure and fluorescence preservation,high-resolution and rapid whole-brain optical imaging,and image post-processing.The cytoarchitectonic information of the entire macaque brain was acquired with a voxel size of 0.32 μm × 0.32 μm × 10 μm,showing its anatomical structure with cell distribution,density,and shape.Furthermore,thanks to viral labeling,individual long-distance projection axons from the frontal cortex were for the first time reconstructed across the entire brain hemisphere with a voxel size of 0.65 μm × 0.65 μm × 3 μm.Our results show that individual cortical axons originating from the prefrontal cortex simultaneously target multiple brain regions,including the visual cortex,striatum,thalamus,and midbrain.This pipeline provides an efficient method for cellular and circuitry investigation of the whole macaque brain with individual-axon resolu-tion,and can shed light on brain function and disorders.