Single-cell transcriptomic evidence for dense intracortical neuropeptide networks

Elife. 2019 Nov 11;8:e47889. 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.

Keywords: mouse; neocortex; neuromodulation; neuron types; neuropeptides; neuroscience; synaptic networks; transcriptomics.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Gene Expression Profiling / methods*
  • Gene Regulatory Networks / genetics
  • Homeostasis / genetics
  • Mice
  • Neocortex / cytology
  • Neuronal Plasticity / genetics
  • Neurons / cytology
  • Neurons / metabolism*
  • Neuropeptides / genetics*
  • Protein Precursors / genetics*
  • Receptors, G-Protein-Coupled / genetics*
  • Signal Transduction / genetics
  • Single-Cell Analysis / methods*
  • Visual Cortex / cytology


  • Neuropeptides
  • Protein Precursors
  • Receptors, G-Protein-Coupled