Calretinin positive neurons form an excitatory amplifier network in the spinal cord dorsal horn

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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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
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 (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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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
165961Modulating cutaneous afferent input: Identifying a source of presynaptic (axo-axonic) inputs in the mouse spinal dorsal hornDavid I HughesBiotechnology and Biological Sciences Research Council (BBSRC)BB/J000620/1NP - Centre for Neuroscience
174050Determining the role of calretinin-RorB spinal interneurons in modulating mechanical painDavid I HughesBiotechnology and Biological Sciences Research Council (BBSRC)BB/P007996/1Institute of Neuroscience & Psychology