Expression of cholecystokinin by neurons in mouse spinal dorsal horn

Gutierrez-Mecinas, M. , Bell, A. M. , Shepherd, F., Polgár, E., Watanabe, M., Furuta, T. and Todd, A. J. (2019) Expression of cholecystokinin by neurons in mouse spinal dorsal horn. Journal of Comparative Neurology, 527(11), pp. 1857-1871. (doi: 10.1002/cne.24657) (PMID:30734936) (PMCID:PMC6563475)

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Excitatory interneurons account for the majority of dorsal horn neurons, and are required for perception of normal and pathological pain. We have identified largely non-overlapping populations in laminae I-III, based on expression of substance P, gastrin-releasing peptide, neurokinin B and neurotensin. Cholecystokinin (CCK) is expressed by many dorsal horn neurons, particularly in the deeper laminae. Here we have used immunocytochemistry and in situ hybridisation to characterise the CCK cells. We show that they account for ~7% of excitatory neurons in laminae I-II, but between a third and a quarter of those in lamina III. They are largely separate from the neurokinin B, neurotensin and gastrin-releasing peptide populations, but show limited overlap with the substance P cells. Laminae II-III neurons with protein kinase Cγ (PKCγ) have been implicated in mechanical allodynia following nerve injury, and we found that around 50% of CCK cells were PKCγ-immunoreactive. Neurotensin is also expressed by PKCγ cells, and among neurons with moderate to high levels of PKCγ, ~85% expressed CCK or neurotensin. A recent transcriptomic study (Häring et al, Nat. Neurosci., 2018) identified mRNA for thyrotropin-releasing hormone (TRH) in a specific subpopulation of CCK neurons, and we show that these account for half of the CCK/PKCγ cells. These findings indicate that CCK cells are distinct from other excitatory interneuron populations that we have defined. They also show that PKCγ cells can be assigned to different classes based on neuropeptide expression, and it will be important to determine the differential contribution of these classes to neuropathic allodynia.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Bell, Mr Andrew and Beresford-Polgar, Dr Erika and Todd, Professor Andrew and Gutierrez-Mecinas, Dr Maria
Authors: Gutierrez-Mecinas, M., Bell, A. M., Shepherd, F., Polgár, E., Watanabe, M., Furuta, T., and Todd, A. J.
College/School:College of Medical Veterinary and Life Sciences > School of Psychology & Neuroscience
College of Medical Veterinary and Life Sciences > School of Biodiversity, One Health & Veterinary Medicine
Journal Name:Journal of Comparative Neurology
ISSN (Online):1096-9861
Published Online:08 February 2019
Copyright Holders:Copyright © 2019 The Authors
First Published:First published in Journal of Comparative Neurology 527(11): 1857-1871
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