Visualizing the itch-sensing skin arbors

ABSTRACT Diverse sensory neurons exhibit distinct neuronal morphologies with a variety of axon terminal arborizations used to subserve their functions. Due to its clinical significance, the molecular and cellular mechanisms of itch are being intensely studied. However, a complete analysis of itch-sensing terminal arborization morphology is missing. Using a novel MrgprC11 CreERT2 transgenic mouse line, we labeled a small subset of itch-sensing neurons that express multiple itch-related molecules including MrgprA3, MrgprC11, histamine receptor H1, IL-31 receptor, 5-HT receptor 1F, natriuretic precursor peptide B, and neuromedin B. By combining sparse genetic labeling and whole-mount PLAP histochemistry, we found that itch-sensing skin arbors exhibit free endings with extensive axonal branching in the superficial epidermis and large receptive fields. These results revealed the unique morphological characteristics of itch-sensing neurons and provide novel insights into the basic mechanisms of itch transmission.