​​​​『BICCN Column』Nature Human neocortex expansion and glutamatergic neuron diversification

Written | November https:// column | General introduction: Cerebral cortex motor neuron map landscape and database alliance BICCN; "BICCN column" Nature | Compared with mice, the single-cell DNA methylation profile of mouse brain has a significant increase in the volume of the human cerebral cortex.
The cerebral cortex is very important for a variety of human cognitive functions.
It will be affected when the cerebral cortex is affected.
Cause a variety of neurological and neuropsychiatric diseases
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A distinctive feature of the human neocortex is that the expansion of its surface area, volume, and number of neurons is out of proportion to the expansion of the subcortical structure, which is why human cognitive activities are more sophisticated and complex
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The cerebral cortex includes the upper granular layer (Supragranular layers), the granular layer and the lower granular layer.
Gene regulation of the neuronal cell diversity in the upper granular layer [1]
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Single-cell transcriptome analysis of human and mouse neocortex shows that the diversity of upper granular glutamate neurons in human neocortex increases, and the function of these neurons also has a significant gradient depending on the depth of the neocortex [2 】
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But the relationship between the diversity of its transcriptome and its functional diversity and anatomical diversity is still unknown
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On October 6, 2021, the BICCN Consortium published an article entitled Human neocortical expansion involves glutamatergic neuron diversification.
As one of the 16 blockbuster articles published jointly, this work uses single-cell omics Patch-seq and other methods to uncover new humans The link between cortical expansion and the diversity of glutamatergic neurons
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There are significant differences in the size and density of neurons in the L2 and L3 regions of the human cortex and the corresponding brain regions of mice (Figure 1).
A previous RNA-seq sequencing study showed that the upper granular layer contains a variety of Cell type, which lays the foundation for further subdivision of cell types in the cortex
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In addition, previous studies have shown that human neocortical slices can still be used for patch clamp experiments on brain slices after twelve hours or more [3,4], based on this BICCN alliance to develop a robust Patch-seq platform [5] , Can perform standardized electrical stimulation, biocytin filling and RNA-seq analysis on brain slices obtained from surgery
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Figure 1 Comparison of human cerebral cortex and mouse cerebral cortex.
Through the Patch-seq platform, the BICCN alliance confirmed that the cell classification obtained is consistent with the results obtained by the transcriptome classification method obtained by nuclear isolation, which proves the difference in Patch-seq The validity of electrophysiological signals as a classification standard for cortical neurons
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The 385 neurons that passed the quality control of transcriptome data can be divided into five types of glutamatergic neurons.
The biggest difference between these types of neurons is the size of dendrites
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Through the analysis of transcription, it is found that there is a strong correlation between the depth of the cell body and the memory expression pattern in different types of neurons.
More than half of the neuron classification features are deeply related to their location
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The differences between different types of neurons are also shown in electrophysiological and morphological characteristics (Figure 2)
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Figure 2 The transcriptional characteristics and positional correlation of different types of glutamatergic neurons.
Human cortical cell diversity has always been difficult to quantitatively define, because of the lack of exploration tools for different cell types and high requirements for data analysis capabilities
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In general, this work uses the Patch-seq work platform to analyze cortical neurosurgery slices, which can enrich neuronal morphology and electrophysiological information on the basis of transcriptome classification, and provide a significant impact on the diversity of human cortical neurons.
Continuous features are defined quantitatively
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In addition, this work serves as an important supplement to the information of cortical neurons in the BICCN alliance, increasing people's understanding of the characteristics and functions of cortical neurons
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Original link: https://doi.
org/10.
1038/s41586-021-03813-8 Platemaker: 11 References 1 Won, H.
, Huang, J.
, Opland, CK, Hartl, CL & Geschwind, DH Human evolved regulatory elements modulate genes involved in cortical expansion and neurodevelopmental disease susceptibility.
Nature communications 10, 2396, doi:10.
1038/s41467-019-10248-3 (2019).
2 Hodge, RD et al.
Conserved cell types with divergent features in human versus mouse cortex.
Nature 573, 61-68, doi:10.
1038/s41586-019-1506-7 (2019).
3 Ting, JT et al.
A robust ex vivo experimental platform for molecular-genetic dissection of adult human neocortical cell types and circuits.
Scientific reports 8, 8407, doi:10.
1038/s41598-018-26803-9 (2018).
4 Gidon, A.
et al.
Dendritic action potentials and computation in human layer 2/3 cortical neurons.
Science (New York , NY) 367, 83-87, doi:10.
1126/science.
aax6239 (2020).
5 Cadwell, CR et al.
Electrophysiological, transcriptomic and morphologic profiling of single neurons using Patch-seq.
Nature biotechnology 34, 199-203, doi:10.
1038/nbt.
3445 (2016).
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