Spinal cord interneurons expressing the gastrin-releasing peptide receptor convey itch through VGLUT2-mediated signaling
| Autor: | Bejan, Aresh, Fabio B, Freitag, Sharn, Perry, Edda, Blümel, Joey, Lau, Marina C M, Franck, Malin C, Lagerström |
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| Rok vydání: | 2017 |
| Předmět: |
Male
genetic structures Vesicular Inhibitory Amino Acid Transport Proteins Green Fluorescent Proteins Calcium imaging Mice Transgenic Conditional knockout analysis Gastrin-releasing peptide receptor population Severity of Illness Index Itch Membrane Potentials Mice Tracing Interneurons parasitic diseases Neuronal networks otorhinolaryngologic diseases Animals Labeled line of itch skin and connective tissue diseases Pain Measurement Spinal cord Pruritus eye diseases Vesicular glutamate transporter 2 Receptors Bombesin Electrophysiology Natriuretic polypeptide B Animals Newborn Vesicular Glutamate Transport Protein 2 Calcium Female Signal Transduction Research Paper |
| Zdroj: | Pain |
| ISSN: | 1872-6623 |
| Popis: | Supplemental Digital Content is Available in the Text. Gastrin-releasing peptide receptor–expressing cells are interneurons that use glutamate to transmit the perception of chemical itch to the next step in the labeled line of itch in the spinal cord. Itch is a sensation that promotes the desire to scratch, which can be evoked by mechanical and chemical stimuli. 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 predominantly excitatory interneurons that are found in the dorsal lamina, especially in laminae II-IV. Application of the specific agonist gastrin-releasing peptide 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 and attenuated responses to both histaminergic and nonhistaminergic agents. We could also show that application of the itch-inducing peptide, natriuretic polypeptide B, induces calcium influx in a subpopulation of Grpr-Cre neurons. To summarize, 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. |
| Databáze: | OpenAIRE |
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