November 29, 2020

Pain and itch processing by subpopulations of molecularly diverse spinal and trigeminal projection neurons

A remarkable molecular and functional heterogeneity of the primary sensory neurons and dorsal horn interneurons transmits pain- and or itch-relevant information, but the molecular signature of the projection neurons that convey the messages to the brain is unclear. Here, using retro-TRAP (translating ribosome affinity purification) and RNA-seq we reveal extensive molecular diversity of spino- and trigeminoparabrachial projection neurons, which to date are almost exclusively defined by their expression of the neurokinin 1 receptor (NK1R).

Among the many genes identified, we highlight distinct subsets of Cck+, Nptx2+, Nmb+, and Crh+ expressing projection neurons. By combining in situ hybridization of retrogradely labeled neurons with Fos-based assays we also demonstrate significant functional heterogeneity, including both convergence and segregation of pain- and itch-provoking inputs onto molecularly diverse subsets of NK1R- and non-NK1R-expressing projection neurons.

The current study provides the first comprehensive investigation into the molecular profiles and functional properties of projection neuron subtypes.

 bioRxiv Subject Collection: Neuroscience

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