To decipher the organizational logic of complex brain circuits,it is important to chart long-distance pathways while preserving micron-level accuracy of local network.However,mapping the neuronal projections with indi...To decipher the organizational logic of complex brain circuits,it is important to chart long-distance pathways while preserving micron-level accuracy of local network.However,mapping the neuronal projections 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 0.32μm×0.32μm×10μm,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 0.65μm×0.65μm×3μm.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 resolution,and can shed light on brain function and disorders.展开更多
基金supported by the National Basic Research Program of China(973 Project2015CB755602)+3 种基金the National Natural Science Foundation of China(61721092,61890953,31871088,and 81871082)Key-Area Research and Development Program of Guangdong Province(2019B030335001)CAMS Innovation Fund for Medical Sciences(2019-I2M-5-014)the Director Fund of Wuhan National Laboratory for Optoelectronics。
文摘To decipher the organizational logic of complex brain circuits,it is important to chart long-distance pathways while preserving micron-level accuracy of local network.However,mapping the neuronal projections 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 0.32μm×0.32μm×10μm,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 0.65μm×0.65μm×3μm.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 resolution,and can shed light on brain function and disorders.
