Human prefrontal cortex (hPFC) is a complex brain region involved in cognitive and emotional processes and several psychiatric disorders. Here, we present an overview of the distribution of the peptidergic systems in 17 subregions of hPFC and three reference cortices obtained by microdissection and based on RNA sequencing and RNAscope methods integrated with published single-cell transcriptomics data. We detected expression of 60 neuropeptides and 60 neuropeptide receptors in at least one of the hPFC subregions. The results reveal that the peptidergic landscape in PFC consists of closely located and functionally different subregions with unique peptide/transmitter–related profiles. Neuropeptide-rich PFC subregions were identified, encompassing regions from anterior cingulate cortex/orbitofrontal gyrus. Furthermore, marked differences in gene expression exist between different PFC regions (>5-fold; cocaine and amphetamine–regulated transcript peptide) as well as between PFC regions and reference regions, for example, for somatostatin and several receptors. We suggest that the present approach allows definition of, still hypothetical, microcircuits exemplified by glutamatergic neurons expressing a peptide cotransmitter either as an agonist (hypocretin/orexin) or antagonist (galanin). Specific neuropeptide receptors have been identified as possible targets for neuronal afferents and, interestingly, peripheral blood-borne peptide hormones (leptin, adiponectin, gastric inhibitory peptide, glucagon-like peptides, and peptide YY). Together with other recent publications, our results support the view that neuropeptide systems may play an important role in hPFC and underpin the concept that neuropeptide signaling helps stabilize circuit connectivity and fine-tune/modulate PFC functions executed during health and disease.

中文翻译：

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人类前额叶皮层的神经肽景观

人类前额叶皮层 (hPFC) 是一个复杂的大脑区域，涉及认知和情绪过程以及多种精神疾病。在这里，我们概述了肽能系统在 hPFC 的 17 个子区域和三个参考皮质中的分布，这些皮质是通过显微解剖获得的，并基于 RNA 测序和 RNAscope 方法与已发表的单细胞转录组学数据相结合。我们在至少一个 hPFC 子区域中检测到 60 种神经肽和 60 种神经肽受体的表达。结果表明，PFC 中的肽能景观由位置紧密且功能不同的子区域组成，具有独特的肽/递质相关概况。鉴定出富含神经肽的 PFC 亚区，包括来自前扣带皮层/眶额回的区域。此外，不同 PFC 区域（> 5 倍；可卡因和苯丙胺调节的转录肽）之间以及 PFC 区域和参考区域之间存在基因表达的显着差异，例如，对于生长抑素和几种受体。我们建议，目前的方法允许定义仍然假设的微电路，例如谷氨酸能神经元表达肽共递质作为激动剂（hypocretin/orexin）或拮抗剂（甘丙肽）。特定的神经肽受体已被确定为神经元传入的可能目标，有趣的是，外周血源性肽激素（瘦素、脂联素、胃抑制肽、胰高血糖素样肽和肽 YY）。连同其他最近的出版物，