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.
The present study is an analysis of a large transcriptomic dataset that is now freely available for download in its entirety athttp://celltypes.brain-map.org/rnaseq/ and is described fully in a rigorously peer-reviewed publication (Tasic, et al., Nature 563:72-78, 2018). All code and intermediate data products involved in preparing this manuscript are freely available from a well-documented GitHub repository: https://github.com/AllenInstitute/PeptidergicNetworks
Article and author information
National Institutes of Health (R01NS092474)
- Stephen J Smith
National Institutes of Health (R01MH104227)
- Stephen J Smith
National Institutes of Health (1U24NS109113)
- Stephen J Smith
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
- David D Ginty, Harvard Medical School, United States
- Received: April 23, 2019
- Accepted: November 10, 2019
- Accepted Manuscript published: November 11, 2019 (version 1)
- Version of Record published: November 27, 2019 (version 2)
© 2019, Smith et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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