Spinal Cord Interneurons Expressing the Gastrin Releasing Peptide Receptor Convey Itch through VGLUT2-mediated Signaling
(English)Manuscript (preprint) (Other academic)
Itch is a sensation that promotes the desire to scratch, which can be evoked by mechanical and chemical stimuli as well as being part of our grooming process. In the spinal cord, neurons expressing the gastrin releasing peptide receptor (GRPR) have been identified as specific mediators of itch. However, our understanding of the GRPR-population in the spinal cord, and thus how these neurons exercise their functions, is limited. For this purpose, we constructed a Cre line designed to target the GRPR population of neurons (Grpr-Cre). Our analysis revealed that Grpr-Cre cells in the spinal cord are predominately excitatory interneurons that are found in the dorsal lamina, especially in lamina II-IV. Application of the specific agonist gastrin releasing peptide (GRP) induced spike responses in 43.3% of the patched Grpr-Cre neurons, where the majority of the cells displayed a tonic firing property. Additionally, our analysis showed that the Grpr-Cre population expresses Vglut2 mRNA and mice ablated of Vglut2 in Grpr-Cre cells (Vglut2-lox;Grpr-Cre mice) displayed less spontaneous itch in their grooming behavior, and attenuated responses to both histaminergic and non-histaminergic agents. Thus, our data indicate that the Grpr-Cre spinal cord neural population is composed of interneurons that use VGLUT2-mediated signaling for transmitting chemical and spontaneous itch stimuli to the next, currently unknown, neurons in the labeled line of itch.
Spinal cord, Grpr, VGLUT2
Medical and Health Sciences
Research subject Medical Science
IdentifiersURN: urn:nbn:se:uu:diva-284058OAI: oai:DiVA.org:uu-284058DiVA: diva2:919693