Transcriptomic evidence for dense peptidergic neuromodulation networks in mouse cortex

Smith, S. J.; Sumbul, U.; Graybuck, L. T.; Collman, F.; Seshamani, S.; Gala, R.; Gliko, O.; Elabbady, L.; Miller, J.; Bakken, T.; Yao, Z.; Lein, E.; Zeng, H.; Tasic, B.; Hawrylycz, M.

doi:10.1101/519694

bioRxiv · 10.1101/519694

Transcriptomic evidence for dense peptidergic neuromodulation networks in mouse cortex

Smith, S. J.·Sumbul, U.·Graybuck, L. T.·Collman, F.·Seshamani, S.·Gala, R.·Gliko, O.·Elabbady, L.·Miller, J.·Bakken, T.·Yao, Z.·Lein, E.·Zeng, H.·Tasic, B.·Hawrylycz, M.

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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.\n\nImpactSingle-cell mRNA sequencing data from mouse neocortex expose evidence for peptidergic neuromodulatory networks that locally interconnect every cortical neuron\n\nData HighlightsO_LIAt least 97% of mouse neocortical neurons express one or more of 18 neuropeptide precursor proteins (NPP) genes at very high levels\nC_LIO_LIAt 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 genes\nC_LIO_LINeocortical 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 power\nC_LIO_LINeuron-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\nC_LI

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Smith, S. J., Sumbul, U., Graybuck, L. T., Collman, F., Seshamani, S., Gala, R., Gliko, O., Elabbady, L., Miller, J., Bakken, T., Yao, Z., Lein, E., Zeng, H., Tasic, B., Hawrylycz, M.. 2019-01-13. Transcriptomic evidence for dense peptidergic neuromodulation networks in mouse cortex. https://doi.org/10.1101/519694

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