10.7554/elife.47889

eLife 2019 167 cites
2019:82020:132021:182022:222023:252024:272025:282026:26
2019 2026
167

Smith, Stephen J and S{\"u}mb{\"u}l, Uygar and Graybuck, Lucas T and Collman, Forrest and Seshamani, Sharmishtaa and Gala, Rohan and Gliko, Olga and Elabbady, Leila and Miller, Jeremy A and Bakken, Trygve E and Rossier, Jean and Yao, Zizhen and Lein, Ed and Zeng, Hongkui and Tasic, Bosiljka and Hawrylycz, Michael

Abstract

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.

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