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Single-Cell Transcriptomic Evidence for Dense Intracortical Neuropeptide Networks

By Stephen J Smith, Uygar Sumbul, Lucas Graybuck, Forrest Collman, Sharmishtaa Seshamani, Rohan Gala, Olga Gliko, Leila Elabbady, Jeremy Miller, Trygve E Bakken, Jean Rossier, Zizhen Yao, Ed Lein, Hongkui Zeng, Bosiljka Tasic, Michael J Hawrylycz

Posted 13 Jan 2019
bioRxiv DOI: 10.1101/519694

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.

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