Spinal lumbar Urocortin 3-expressing neurons are associated with both scratching and Compound 48/80-induced sensations.

Urocortin 3 is a neuropeptide that belongs to the corticotropin-releasing hormone family and is involved in mechanosensation and stress regulation. In this study, we show that Urocortin 3 marks a population of excitatory neurons in the mouse spinal cord, divided into 2 nonoverlapping subpopulations expressing protein kinase C gamma or calretinin/calbindin 2, populations previously associated with mechanosensation. Electrophysiological experiments demonstrated that lumbar spinal Urocortin 3 neurons receive both glycinergic and GABAergic local tonic inhibition, and monosynaptic inputs from both Aβ and C fibers, which could be confirmed by retrograde trans-synaptic rabies tracing. Furthermore, fos analyses showed that subpopulations of lumbar Urocortin 3 neurons are activated by artificial scratching or Compound 48/80-induced sensations. Chemogenetic activation of lumbar Urocortin 3-Cre neurons evoked a targeted biting/licking behavior towards the corresponding dermatome and chemogenetic inhibition decreased Compound 48/80-induced behavior. Hence, spinal lumbar Urocortin 3 neurons represent a mechanically associated population with roles in both scratching and Compound 48/80-induced sensations.