Single-cell transcriptomic evidence for dense intracortical neuropeptide networks

Area of Science:

• Neuroscience
• Molecular Biology
• Genomics

Background:

• Cortical synaptic networks are fundamental to brain function, involving complex processes like homeostasis, modulation, and plasticity.
• Understanding the molecular mechanisms underlying these processes is crucial for advancing neuroscience.

Purpose of the Study:

• To investigate the molecular underpinnings of neuropeptide signaling in cortical neurons.
• To identify distinct neuropeptidergic networks and their potential roles in cortical function.

Main Methods:

• Single-cell RNA sequencing (scRNA-seq) of 22,439 mouse neocortical neurons.
• Transcriptomic analysis to identify gene expression patterns of neuropeptide precursors (NPPs) and neuropeptide-selective G-protein-coupled receptors (NP-GPCRs).

Main Results:

• Discovery of transcriptomic evidence for dozens of distinct neuropeptidergic modulatory networks interconnecting cortical neurons.
• Identification that transcripts for NPPs and NP-GPCRs are highly abundant in nearly all cortical neurons.
• Analysis revealed diverse subsets of NP signaling genes expressed by individual neurons, forming 37 potential NPP/NP-GPCR signaling pairs.

Conclusions:

• Cortical neurons extensively utilize neuropeptide signaling pathways.
• Neuropeptidergic networks likely play significant roles in maintaining cortical homeostasis and plasticity.
• Neuron-type-specific gene expression patterns provide testable predictions for 37 peptidergic neuromodulatory networks.