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Single-Cell Transcriptomic Evidence for Dense Intracortical Neuropeptide Networks

By Stephen J Smith, Uygar Sümbül, Lucas T. Graybuck, Forrest Collman, Sharmishtaa Seshamani, Rohan Gala, Olga Gliko, Leila Elabbady, Jeremy A. Miller, Trygve Bakken, Jean Rossier, Zizhen Yao, Ed Lein, Hongkui Zeng, Bosiljka Tasic, Michael Hawrylycz

Posted 13 Jan 2019
bioRxiv DOI: 10.1101/519694 (published DOI: 10.7554/eLife.47889)

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. Impact Single-cell mRNA sequencing data from mouse neocortex expose evidence for peptidergic neuromodulatory networks that locally interconnect every cortical neuron Data Highlights

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