Spatio-molecular gene expression reflects dorsal anterior cingulate cortex structure and function in the human brain

Area of Science:

• Neuroscience
• Molecular Biology
• Genomics

Background:

• The dorsal anterior cingulate cortex (dACC) is crucial for cognitive control, reward processing, and emotional regulation.
• Evolutionarily older than the dorsolateral prefrontal cortex (dlPFC), the dACC possesses unique specializations like agranularity and von Economo neurons (VENs).

Purpose of the Study:

• To define cell types and spatial domains within the dACC using advanced transcriptomic techniques.
• To compare the molecular and laminar specialization of the dACC with the dlPFC.

Main Methods:

• Paired spatially resolved transcriptomics (SRT) and single-nucleus RNA-sequencing (snRNA-seq) were performed on ten adult neurotypical human brain samples.
• Non-negative matrix factorization was employed to project gene expression patterns from snRNA-seq onto SRT data for spatial localization.
• Publicly available resources were used to analyze spatial topography, disease risk enrichment, and connectivity of dACC cell types, including VENs.

Main Results:

• Detailed mapping of cell types and their spatial distribution within the dACC was achieved.
• Inferred spatial localization revealed specific topographical arrangements of neuronal and glial populations.
• Comparative analysis highlighted distinct laminar and molecular specializations between the dACC and dlPFC.

Conclusions:

• This study provides a high-resolution spatial map of cell types in the human dACC, revealing its unique molecular architecture.
• The findings offer insights into the cellular basis of cognitive and emotional functions regulated by the dACC and its specialized cell types like VENs.
• The comparative analysis with dlPFC deepens our understanding of regional specialization within the human cortex.