eLife (Nov 2019)

Single-cell transcriptomic evidence for dense intracortical neuropeptide networks

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

DOI
https://doi.org/10.7554/eLife.47889
Journal volume & issue
Vol. 8

Abstract

Read online

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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