%0 Journal Article %T Single-cell transcriptomic evidence for dense intracortical neuropeptide networks. %A Smith SJ %A Sümbül U %A Graybuck LT %A Collman F %A Seshamani S %A Gala R %A Gliko O %A Elabbady L %A Miller JA %A Bakken TE %A Rossier J %A Yao Z %A Lein E %A Zeng H %A Tasic B %A Hawrylycz M %J Elife %V 8 %N 0 %D 11 2019 11 %M 31710287 %F 8.713 %R 10.7554/eLife.47889 %X Seeking new insights into the homeostasis, modulation and plasticity of cortical synaptic networks, we have analyzed results from a single-cell RNA-seq study of 22,439 mouse neocortical neurons. Our analysis exposes transcriptomic evidence for dozens of molecularly distinct neuropeptidergic modulatory networks that directly interconnect all cortical neurons. This evidence begins with a discovery that transcripts of one or more neuropeptide precursor (NPP) and one or more neuropeptide-selective G-protein-coupled receptor (NP-GPCR) genes are highly abundant in all, or very nearly all, cortical neurons. Individual neurons express diverse subsets of NP signaling genes from palettes encoding 18 NPPs and 29 NP-GPCRs. These 47 genes comprise 37 cognate NPP/NP-GPCR pairs, implying the likelihood of local neuropeptide signaling. Here, we use neuron-type-specific patterns of NP gene expression to offer specific, testable predictions regarding 37 peptidergic neuromodulatory networks that may play prominent roles in cortical homeostasis and plasticity.