In a study published today in the US-based journal PNAS, insights regarding the chemical anatomy of the human prefrontal cortex are described. In particular, a wide spectrum of peptidergic systems is explored that may finetune/modulate functions that are executed in this part of the brain during health and disease. The project was conducted by an international team with researchers from Karolinska Institutet (Sweden), SciLifeLab, KTH-Royal Institute of Technology, Linköping University, the Human Brain Tissue Bank (Hungary) and McGill University (Canada).

The human prefrontal cortex (hPFC), the most rostral part of the frontal lobe, is highly developed in the brain and involved in multiple complex functions, including cognitive processes, e.g. working memory and decision making as well as generation and regulation of emotions, and is also thought to be of significance in pathological processes of many psychiatric disorders.

The analysis described in the paper is based on RNA-seq gene expression profiling of 165 micro-dissected samples from 17 hPFC subregions and three reference cortices (frontal, parietal and temporal cortex), obtained from both male and female donors, including both left and right hemispheres. The resource is released as part of the new version of the HPA Brain Atlas and are complemented with RNAscope and published single-cell transcriptomics data for the analysis of cellular localization.

The study suggests that the well-established anatomical and functional heterogeneity of the human PFC is also reflected in the expression pattern of the neuropeptides. Neuropeptide-rich PFC subregions were also identified, including the cingulate and orbital compartments from the more dorsal and lateral portions of the PFC. It is proposed that the neuropeptide receptors represent potential targets for drug development.

The study was supported by the Knut and Alice Wallenberg Foundation, the Swedish Research Council, the Hungarian Brain Research Program and the SciLifeLab & Wallenberg Data Driven Life Science Program.

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