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

## TL;DR

Spinal neurons that produce Urocortin 3 are linked to scratching and Compound 48/80-induced sensations in mice.

## Contribution

Identifies Urocortin 3-expressing spinal neurons as a novel population involved in mechanosensation and itch-related behaviors.

## Key findings

- Urocortin 3 neurons in the lumbar spinal cord are activated by scratching or Compound 48/80.
- Chemogenetic inhibition of these neurons reduces Compound 48/80-induced behaviors.
- These neurons receive inputs from Aβ and C fibers and are inhibited by glycinergic and GABAergic signals.

## Abstract

Supplemental Digital Content is Available in the Text.

Lumbar spinal Urocortin 3 neurons express markers associated with mechanosensation and subpopulations are activated by scratching or Compound 48/80. Inhibition reduced the response to Compound 48/80.

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.