Single-cell transcriptomic evidence for dense intracortical neuropeptide networks

Author:

Smith Stephen J1ORCID,Sümbül Uygar1ORCID,Graybuck Lucas T1ORCID,Collman Forrest1ORCID,Seshamani Sharmishtaa1,Gala Rohan1ORCID,Gliko Olga1ORCID,Elabbady Leila1ORCID,Miller Jeremy A1ORCID,Bakken Trygve E1ORCID,Rossier Jean2ORCID,Yao Zizhen1,Lein Ed1ORCID,Zeng Hongkui1ORCID,Tasic Bosiljka1ORCID,Hawrylycz Michael1ORCID

Affiliation:

1. Allen Institute for Brain Science, Seattle, United States

2. Neuroscience Paris Seine, Sorbonne Université, Paris, France

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.

Funder

National Institutes of Health

Publisher

eLife Sciences Publications, Ltd

Subject

General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Medicine,General Neuroscience

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