Disentangling Transcriptomic Heterogeneity Within the Human Subgenual Anterior Cingulate Cortex

The subgenual anterior cingulate cortex (sgACC) is a critical site for understanding the neural correlates of affect and emotion. While the activity of the sgACC is functionally homogenous, it is comprised of multiple Brodmann Areas (BAs) that possess different cytoarchitectures. In some sgACC BAs, Layer 5 is sublaminated into L5a and L5b which has implications for its projection targets. To understand how the transcriptional profile differs between the BAs, layers, and sublayers of human sgACC, we collected layer strips using laser capture microdissection followed by RNA sequencing. We found no significant differences in transcript expression in these specific cortical layers between BAs within the sgACC. In contrast, we identified striking differences between Layers 3 and 5a or 5b that were concordant across sgACC BAs. We found that sublayers 5a and 5b were transcriptionally similar. Pathway analyses of L3 and L5 revealed overlapping biological processes related to synaptic function. However, L3 was enriched for pathways related to cell-to-cell junction and dendritic spines whereas L5 was enriched for pathways related to brain development and presynaptic function, indicating potential functional differences across layers. Our study provides important insight into normative transcriptional features of the sgACC.