Characterisation of deep dorsal horn projection neurons in the spinal cord of the Phox2a::Cre mouse line

Kókai, É., Alsulaimain, W. A.A., Dickie, A. C., Bell, A. M. , Goffin, L., Watanabe, M., Gutierrez-Mecinas, M. and Todd, A. J. (2022) Characterisation of deep dorsal horn projection neurons in the spinal cord of the Phox2a::Cre mouse line. Molecular Pain, 18, p. 17448069221119614. (doi: 10.1177/17448069221119614) (PMID:36000342) (PMCID:PMC9445510)

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Abstract

Projection neurons belonging to the anterolateral system (ALS) underlie the perception of pain, skin temperature and itch. Many ALS cells are located in laminae III-V of the dorsal horn and the adjacent lateral white matter. However, relatively little is known about the excitatory synaptic input to these deep ALS cells, and therefore about their engagement with the neuronal circuitry of the region. We have used a recently developed mouse line, Phox2a::Cre, to investigate a population of deep dorsal horn ALS neurons known as "antenna cells", which are characterised by dense innervation from peptidergic nociceptors, and to compare these with other ALS cells in the deep dorsal horn and lateral white matter. We show that these two classes differ, both in the density of excitatory synapses, and in the source of input at these synapses. Peptidergic nociceptors account for around two-thirds of the excitatory synapses on the antenna cells, but for only a small proportion of the input to the non-antenna cells. Conversely, boutons with high levels of VGLUT2, which are likely to originate mainly from glutamatergic spinal neurons, account for only ∼5% of the excitatory synapses on antenna cells, but for a much larger proportion of the input to the non-antenna cells. VGLUT1 is expressed by myelinated low-threshold mechanoreceptors and corticospinal axons, and these innervate both antenna and non-antenna cells. However, the density of VGLUT1 input to the non-antenna cells is highly variable, consistent with the view that these neurons are functionally heterogeneous.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:alsulaiman, Wafa Abdulsalam A and Dickie, Dr Allen and Kokai, Miss Eva and Gutierrez-Mecinas, Dr Maria and Bell, Mr Andrew and Todd, Professor Andrew
Authors: Kókai, É., Alsulaimain, W. A.A., Dickie, A. C., Bell, A. M., Goffin, L., Watanabe, M., Gutierrez-Mecinas, M., and Todd, A. J.
College/School:College of Medical Veterinary and Life Sciences > School of Biodiversity, One Health & Veterinary Medicine
College of Medical Veterinary and Life Sciences > School of Psychology & Neuroscience
Journal Name:Molecular Pain
Publisher:SAGE Publications
ISSN:1744-8069
ISSN (Online):1744-8069
Published Online:24 August 2022
Copyright Holders:Copyright © 2022 The Authors
First Published:First published in Molecular Pain 18: 17448069221119614
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
308174Spinal circuits underlying pathological painAndrew ToddWellcome Trust (WELLCOTR)219433/Z/19/ZCentre for Neuroscience
302893Neuronal circuits for itch in the spinal dorsal hornAndrew ToddMedical Research Council (MRC)MR/S002987/1Centre for Neuroscience