Expression of calretinin among different neurochemical classes of interneuron in the superficial dorsal horn of the mouse spinal cord

Gutierrez-Mecinas, M. , Davis, O., Polgár, E., Shahzad, M., Navarro-Batista, K., Furuta, T., Watanabe, M., Hughes, D. I. and Todd, A. J. (2019) Expression of calretinin among different neurochemical classes of interneuron in the superficial dorsal horn of the mouse spinal cord. Neuroscience, 398, pp. 171-181. (doi: 10.1016/j.neuroscience.2018.12.009) (PMID:30553791) (PMCID:PMC6347472)

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Abstract

Around 75% of neurons in laminae I-II of the mouse dorsal horn are excitatory interneurons, and these are required for normal pain perception. We have shown that four largely non-overlapping excitatory interneuron populations can be defined by expression of the neuropeptides neurotensin, neurokinin B (NKB), gastrin-releasing peptide (GRP) and substance P. In addition, we recently identified a population of excitatory interneurons in glabrous skin territory that express dynorphin. The calcium-binding protein calretinin is present in many excitatory neurons in this region, but we know little about its relation to these neuropeptide markers. Here we show that calretinin is differentially expressed, being present in the majority of substance P-, GRP- and NKB-expressing cells, but not in the neurotensin or dynorphin cells. Calretinin-positive cells have been implicated in detection of noxious mechanical stimuli, but are not required for tactile allodynia after neuropathic pain. Our findings are therefore consistent with the suggestion that neuropathic allodynia involves the neurotensin and/or dynorphin excitatory interneuron populations. Around a quarter of inhibitory interneurons in lamina I-II contain calretinin, and recent transcriptomic studies suggest that these co-express substance P. We confirm this, by showing that inhibitory Cre-expressing cells in a Tac1Cre knock-in mouse are calretinin-immunoreactive. Interestingly, there is evidence that these cells express low levels of peptidylglycine alpha-amidating monooxygenase, an enzyme required for maturation of neuropeptides. This may explain our previous finding that although the substance P precursor preprotachykinin A can be detected in some inhibitory interneurons, very few inhibitory axonal boutons are immunoreactive for substance P.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Hughes, Dr David I and Davis, Olivia and Gutierrez-Mecinas, Dr Maria and Beresford-Polgar, Dr Erika and Todd, Professor Andrew
Authors: Gutierrez-Mecinas, M., Davis, O., Polgár, E., Shahzad, M., Navarro-Batista, K., Furuta, T., Watanabe, M., Hughes, D. I., and Todd, A. J.
College/School:College of Medical Veterinary and Life Sciences
College of Medical Veterinary and Life Sciences > Institute of Neuroscience and Psychology
Journal Name:Neuroscience
Publisher:Elsevier
ISSN:0306-4522
ISSN (Online):1873-7544
Published Online:13 December 2018
Copyright Holders:Copyright © 2018 The Authors
First Published:First published in Neuroscience 398: 171-181
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
644164Defining pain circuitry in health and diseaseAndrew ToddWellcome Trust (WELLCOTR)102645/Z/13/ZINP - CENTRE FOR NEUROSCIENCE
689031The role of NPY-containing inhibitory interneurons in spinal pain pathwaysAndrew ToddBiotechnology and Biological Sciences Research Council (BBSRC)BB/N006119/1INP - CENTRE FOR NEUROSCIENCE
737031Determining the role of calretinin-RorB spinal interneurons in modulating mechanical painDavid I HughesBiotechnology and Biological Sciences Research Council (BBSRC)BB/P007996/1INP - CENTRE FOR NEUROSCIENCE