Single-cell transcriptomic evidence for dense intracortical neuropeptide networks

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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Single-Cell Transcriptomic Evidence for Dense Intracortical Neuropeptide Networks

10.1101/519694 ◽

2019 ◽

Author(s):

Stephen J Smith ◽

Uygar Sümbül ◽

Lucas Graybuck ◽

Forrest Collman ◽

Sharmishtaa Seshamani ◽

...

Keyword(s):

Single Cell ◽

G Protein ◽

Cortical Neurons ◽

Expression Patterns ◽

List Type ◽

Neuron Type ◽

Sequencing Data ◽

G Protein Coupled Receptor ◽

Neocortical Neurons ◽

G Protein Coupled

SummarySeeking 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.ImpactSingle-cell mRNA sequencing data from mouse neocortex expose evidence for peptidergic neuromodulatory networks that locally interconnect every cortical neuronData HighlightsAt least 97% of mouse neocortical neurons express one or more of 18 neuropeptide precursor proteins (NPP) genes at very high levelsAt least 98% of cortical neurons express one or more of 29 neuropeptide-selective G-protein-coupled receptor (NP-GPCR) genes cognate to the 18 highly expressed NPP genesNeocortical expression of these 18 NPP and 29 NP-GPCR genes is highly neuron-type-specific and their expression patterns differentiate transcriptomic neuron types with exceptional powerNeuron-type taxonomy and type-specific expression of 37 cognate NPP / NP-GPCR gene pairs generate testable predictions of at least 37 local intracortical neuromodulation networks

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