Abstract
Briefly Analysis of single-cell RNA-Seq data from mouse neocortex exposes evidence for local neuropeptidergic modulation networks that involve every cortical neuron directly.
Data Highlights
At least 98% of mouse neocortical neurons express one or more of 18 neuropeptide precursor proteins (NPP) genes.
At least 98% of cortical neurons express one or more of 29 neuropeptide-selective G-protein-coupled receptor (NP-GPCR) genes.
Neocortical expression of these 18 NPP and 29 NP-GPCR genes is highly neuron-type-specific and permits exceptionally powerful differentiation of transcriptomic neuron types.
Neuron-type-specific expression of 37 cognate NPP / NP-GPCR gene pairs predicts modulatory connectivity within 37 or more neuron-type-specific intracortical networks.
Summary Seeking insight into homeostasis, modulation and plasticity of cortical synaptic networks, we analyzed results from deep RNA-Seq analysis of 22,439 individual mouse neocortical neurons. This work exposes transcriptomic evidence that all cortical neurons participate directly in highly multiplexed networks of modulatory neuropeptide (NP) signaling. The 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 nearly all cortical neurons. Individual neurons express diverse subsets of NP signaling genes drawn from a palette encoding 18 NPPs and 29 NP-GPCRs. Remarkably, these 47 genes comprise 37 cognate NPP/NP-GPCR pairs, implying a strong likelihood of dense, cortically localized neuropeptide signaling. Here we use neuron-type-specific NP gene expression signatures to put forth specific, testable predictions regarding 37 peptidergic neuromodulatory networks that may play prominent roles in cortical homeostasis and plasticity.