Smith, K. M. et al. (2019) Calretinin positive neurons form an excitatory amplifier network in the spinal cord dorsal horn. eLife, 8, e49190. (doi: 10.7554/eLife.49190) (PMID:31713514) (PMCID:PMC6908433)
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203048.pdf - Published Version Available under License Creative Commons Attribution. 7MB |
Abstract
Nociceptive information is relayed through the spinal cord dorsal horn, a critical area in sensory processing. The neuronal circuits in this region that underpin sensory perception must be clarified to better understand how dysfunction can lead to pathological pain. This study used an optogenetic approach to selectively activate spinal interneurons that express the calcium-binding protein calretinin (CR). We show that these interneurons form an interconnected network that can initiate and sustain enhanced excitatory signaling, and directly relay signals to lamina I projection neurons. Photoactivation of CR interneurons in vivo resulted in a significant nocifensive behavior that was morphine sensitive, caused a conditioned place aversion, and was enhanced by spared nerve injury. Furthermore, halorhodopsin-mediated inhibition of these interneurons elevated sensory thresholds. Our results suggest that dorsal horn circuits that involve excitatory CR neurons are important for the generation and amplification of pain and identify these interneurons as a future analgesic target.
| Item Type: | Articles |
|---|---|
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Boyle, Dr Kieran and Hughes, Dr David I and Davis, Olivia |
| Creator Roles: | Davis, O. C.Formal analysis, Investigation, Writing – review and editing Boyle, K. A.Formal analysis, Supervision, Investigation, Methodology, Writing – review and editing Hughes, D. I.Conceptualization, Formal analysis, Supervision, Funding acquisition, Investigation, Methodology, Writing – original draft, Project administration, Writing – review and editing |
| Authors: | Smith, K. M., Browne, T. J., Davis, O. C.,, Coyle, A., Boyle, K. A., Watanabe, M., Dickinson, S. A., Iredale, J. A., Gradwell, M. A., Jobling, P., Callister, R. J., Dayas, C. V., Hughes, D. I., and Graham, B. A. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Psychology & Neuroscience |
| Journal Name: | eLife |
| Publisher: | eLife Sciences Publications |
| ISSN: | 2050-084X |
| ISSN (Online): | 2050-084X |
| Copyright Holders: | Copyright © 2019 Smith et al. |
| First Published: | First published in eLife 8: e49190 |
| Publisher Policy: | Reproduced under a Creative Commons License |
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