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On March 31st, Beijing time, Nature Neuroscience published a research paper titled "Projection Map of Mouse Prefrontal Cortex Single Neuron" in the form of a cover article.
Scientific Research Institute), Shanghai Brain Science and Brain-inspired Research Center, Yan Jun Research Group, Xu Ninglong Research Group of State Key Laboratory of Neuroscience, Suzhou Brain Spatial Information Research Institute of Huazhong University of Science and Technology, and Gong Hui team of Wuhan National Optoelectronics Research Center
.
This research is the first in the field of international mesoscopic atlas to reconstruct the whole-brain projection atlas of 6357 single neurons in the mouse prefrontal cortex, establishing the world's largest database of mouse whole-brain mesoscopic neural connections; the first discovery of mouse prefrontal cortex There are 64 types of neuronal projection subtypes in the lobe cortex, revealing their spatial distribution rules, elucidating the modular connection network and hierarchical structure in the prefrontal cortex, and the correspondence between neuron transcriptome subtypes and projection subtypes, thereby revealing The regularity of internal connections and external projections in the prefrontal cortex, and a possible working model of the prefrontal cortex is proposed
.
This study not only lays a structural foundation for in-depth exploration of the neural mechanisms of advanced cognitive functions, but also provides important technical support for exploring the whole-brain mesoscopic neural connection map
.
The information exchange between different brain regions in the cerebral cortex relies on the long-range projections of neurons, and neurons with different projection patterns often participate in different brain functions
.
Therefore, studying the projection patterns of neurons and their basic laws is of great significance for analyzing the organizational structure and information processing mechanism of the brain
.
Previous studies have extensively studied the whole-brain projections of mouse cortical neurons using population neuron tracing techniques, and found that cortical projection neurons can be divided into medial telencephalon neurons, pyramidal tract neurons, and corticothalamic neurons.
.
However, research in recent years has shown that within these traditional neuron types there are more complex neuron subtypes with finer division of functions
.
The systematic mapping of projection maps at the single neuron level in the brain will help to discover new neuron subtypes and the connection rules of brain networks, so as to more systematically and comprehensively analyze the working principle of the brain
.
To draw the whole-brain projection at the single-neuron level in mammalian brains such as mice requires three-dimensional reconstruction of single-neuron morphology in terabyte (TB)-scale whole-brain optical imaging big data
.
The whole process is labor-intensive, extremely complex and time-consuming, and is an internationally recognized problem
.
In order to solve this problem, Dr.
Gou Lingfeng of Yan Jun's research group has independently developed the TB-level optical imaging big data neuron tracking and analysis software represented by Fast Neurite Tracer (FNT) through years of hard work, which is used for research model animals.
The neural connection map of brain regions establishes a set of research methods and processes
.
The prefrontal cortex plays an important role in high-level cognitive functions such as decision-making, working memory, and attention.
Abnormalities in its structure and function can lead to a variety of brain diseases
.
Prefrontal neurons project a wide range, covering almost most brain regions, including cortex, striatum, thalamus, midbrain, and hindbrain
.
Existing studies have mostly used population neuron tracing techniques to study the brain-wide projection patterns of neurons in the prefrontal cortex.
At the individual neuron level, the regularity of axonal projections of prefrontal neurons is still unclear
.
Although the current study suggests a modular and hierarchical structure between different brain regions in the mouse cortex, the nature of the network of connections within the prefrontal cortex remains to be studied
.
Through cooperation with the team of Gong Hui of Huazhong University of Science and Technology and the whole-brain mesoscopic neural connection mapping platform of the Brain Intelligence Center of Excellence, the study obtained whole-brain imaging data of 161 mice, and reconstructed 6357 single neurons in the prefrontal lobe.
Axonal morphology (Panel A)
.
After obtaining the projection map of a single neuron in the prefrontal lobe, the research team used a self-developed cluster analysis method to quantitatively describe and compare the similarity of neuron axonal morphology, obtained 64 projection subtypes, and mapped these neuron subtypes Distribution in the prefrontal subregions and in the superficial layers of the cortex (Panel B)
.
In addition, the study found that the intra-prefrontal connectivity network has a modular nature and hierarchical structure by establishing a high spatial resolution of the intra-prefrontal connectivity network (Figure C)
.
Through correlation analysis with prefrontal transcriptome data, and using reverse tracing and single-molecule fluorescence in situ hybridization techniques, it was found that a single transcriptome isoform corresponds to an important rule of multiple projection isoforms (Figure D)
.
The research developed the software FNT for efficient reconstruction of neurons in the big data of brain atlas, constructed a single neuron projection map of the mouse prefrontal lobe, and found that there are 64 neuron projection subtypes in the prefrontal lobe and the existence of modules in the internal connection of the prefrontal lobe and hierarchical structure, which provides clues to how the prefrontal cortex works
.
Among them, the rule that a single transcriptome subtype corresponds to multiple projection subtypes further highlights the importance of single neuron projection maps for neuron classification
.
The research work is supported by the Shanghai Municipal Government, the Ministry of Science and Technology, the Chinese Academy of Sciences, and the National Natural Science Foundation of China
.
A.
The distribution of 6357 prefrontal single neurons in prefrontal subregions and the axonal morphology of the whole brain; B.
The morphological classification of neurons, the distribution of 64 prefrontal projection neuron subtypes in prefrontal subregions and cortical depth ; C, Modularity and hierarchical structure of the internal connectivity network in the prefrontal lobe; D, Relationship between prefrontal lobe projection subtypes and genetic subtypes (CT cortical thalamic neurons in the PL-ORB brain area) 195 neurons in the prefrontal lobe of mice Whole Brain Projection Source: Center for Excellence in Brain Science and Intelligent Technology, Chinese Academy of Sciences
Scientific Research Institute), Shanghai Brain Science and Brain-inspired Research Center, Yan Jun Research Group, Xu Ninglong Research Group of State Key Laboratory of Neuroscience, Suzhou Brain Spatial Information Research Institute of Huazhong University of Science and Technology, and Gong Hui team of Wuhan National Optoelectronics Research Center
.
This research is the first in the field of international mesoscopic atlas to reconstruct the whole-brain projection atlas of 6357 single neurons in the mouse prefrontal cortex, establishing the world's largest database of mouse whole-brain mesoscopic neural connections; the first discovery of mouse prefrontal cortex There are 64 types of neuronal projection subtypes in the lobe cortex, revealing their spatial distribution rules, elucidating the modular connection network and hierarchical structure in the prefrontal cortex, and the correspondence between neuron transcriptome subtypes and projection subtypes, thereby revealing The regularity of internal connections and external projections in the prefrontal cortex, and a possible working model of the prefrontal cortex is proposed
.
This study not only lays a structural foundation for in-depth exploration of the neural mechanisms of advanced cognitive functions, but also provides important technical support for exploring the whole-brain mesoscopic neural connection map
.
The information exchange between different brain regions in the cerebral cortex relies on the long-range projections of neurons, and neurons with different projection patterns often participate in different brain functions
.
Therefore, studying the projection patterns of neurons and their basic laws is of great significance for analyzing the organizational structure and information processing mechanism of the brain
.
Previous studies have extensively studied the whole-brain projections of mouse cortical neurons using population neuron tracing techniques, and found that cortical projection neurons can be divided into medial telencephalon neurons, pyramidal tract neurons, and corticothalamic neurons.
.
However, research in recent years has shown that within these traditional neuron types there are more complex neuron subtypes with finer division of functions
.
The systematic mapping of projection maps at the single neuron level in the brain will help to discover new neuron subtypes and the connection rules of brain networks, so as to more systematically and comprehensively analyze the working principle of the brain
.
To draw the whole-brain projection at the single-neuron level in mammalian brains such as mice requires three-dimensional reconstruction of single-neuron morphology in terabyte (TB)-scale whole-brain optical imaging big data
.
The whole process is labor-intensive, extremely complex and time-consuming, and is an internationally recognized problem
.
In order to solve this problem, Dr.
Gou Lingfeng of Yan Jun's research group has independently developed the TB-level optical imaging big data neuron tracking and analysis software represented by Fast Neurite Tracer (FNT) through years of hard work, which is used for research model animals.
The neural connection map of brain regions establishes a set of research methods and processes
.
The prefrontal cortex plays an important role in high-level cognitive functions such as decision-making, working memory, and attention.
Abnormalities in its structure and function can lead to a variety of brain diseases
.
Prefrontal neurons project a wide range, covering almost most brain regions, including cortex, striatum, thalamus, midbrain, and hindbrain
.
Existing studies have mostly used population neuron tracing techniques to study the brain-wide projection patterns of neurons in the prefrontal cortex.
At the individual neuron level, the regularity of axonal projections of prefrontal neurons is still unclear
.
Although the current study suggests a modular and hierarchical structure between different brain regions in the mouse cortex, the nature of the network of connections within the prefrontal cortex remains to be studied
.
Through cooperation with the team of Gong Hui of Huazhong University of Science and Technology and the whole-brain mesoscopic neural connection mapping platform of the Brain Intelligence Center of Excellence, the study obtained whole-brain imaging data of 161 mice, and reconstructed 6357 single neurons in the prefrontal lobe.
Axonal morphology (Panel A)
.
After obtaining the projection map of a single neuron in the prefrontal lobe, the research team used a self-developed cluster analysis method to quantitatively describe and compare the similarity of neuron axonal morphology, obtained 64 projection subtypes, and mapped these neuron subtypes Distribution in the prefrontal subregions and in the superficial layers of the cortex (Panel B)
.
In addition, the study found that the intra-prefrontal connectivity network has a modular nature and hierarchical structure by establishing a high spatial resolution of the intra-prefrontal connectivity network (Figure C)
.
Through correlation analysis with prefrontal transcriptome data, and using reverse tracing and single-molecule fluorescence in situ hybridization techniques, it was found that a single transcriptome isoform corresponds to an important rule of multiple projection isoforms (Figure D)
.
The research developed the software FNT for efficient reconstruction of neurons in the big data of brain atlas, constructed a single neuron projection map of the mouse prefrontal lobe, and found that there are 64 neuron projection subtypes in the prefrontal lobe and the existence of modules in the internal connection of the prefrontal lobe and hierarchical structure, which provides clues to how the prefrontal cortex works
.
Among them, the rule that a single transcriptome subtype corresponds to multiple projection subtypes further highlights the importance of single neuron projection maps for neuron classification
.
The research work is supported by the Shanghai Municipal Government, the Ministry of Science and Technology, the Chinese Academy of Sciences, and the National Natural Science Foundation of China
.
A.
The distribution of 6357 prefrontal single neurons in prefrontal subregions and the axonal morphology of the whole brain; B.
The morphological classification of neurons, the distribution of 64 prefrontal projection neuron subtypes in prefrontal subregions and cortical depth ; C, Modularity and hierarchical structure of the internal connectivity network in the prefrontal lobe; D, Relationship between prefrontal lobe projection subtypes and genetic subtypes (CT cortical thalamic neurons in the PL-ORB brain area) 195 neurons in the prefrontal lobe of mice Whole Brain Projection Source: Center for Excellence in Brain Science and Intelligent Technology, Chinese Academy of Sciences
