Substance P-expressing neurons in the superficial dorsal horn of the mouse spinal cord: insights into their functions and their roles in synaptic circuits

Polgár, E., Bell, A. M. , Gutierrez-Mecinas, M. , Dickie, A. C., Akar, O., Costreie, M., Watanabe, M. and Todd, A. J. (2020) Substance P-expressing neurons in the superficial dorsal horn of the mouse spinal cord: insights into their functions and their roles in synaptic circuits. Neuroscience, 450, pp. 113-125. (doi: 10.1016/j.neuroscience.2020.06.038) (PMID:32634530)

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Abstract

The tachykinin peptide substance P (SP) is expressed by many interneurons and some projection neurons in the superficial dorsal horn of the spinal cord. We have recently shown that SP-expressing excitatory interneurons in lamina II correspond largely to a morphological class known as radial cells. However, little is known about their function, or their synaptic connectivity. Here we use a modification of the Brainbow technique to define the excitatory synaptic input to SP radial cells. We show that around half of their excitatory synapses (identified by expression of Homer) are from boutons with VGLUT2, which are likely to originate mainly from local interneurons. The remaining synapses presumably include primary afferents, which generally have very low levels of VGLUT2. Our results also suggest that the SP cells are preferentially innervated by a population of excitatory interneurons defined by expression of green fluorescent protein under control of the gene for gastrin-releasing peptide, and that they receive sparser input from other types of excitatory interneuron. We show that around 40% of lamina I projection neurons express Tac1, the gene encoding substance P. Finally, we show that silencing Tac1-expressing cells in the dorsal horn results in a significant reduction in reflex responses to cold and radiant heat, but does not affect withdrawal to von Frey hairs, or chloroquine-evoked itch.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Dickie, Dr Allen and Gutierrez-Mecinas, Dr Maria and Bell, Mr Andrew and Beresford-Polgar, Dr Erika and Todd, Professor Andrew
Authors: Polgár, E., Bell, A. M., Gutierrez-Mecinas, M., Dickie, A. C., Akar, O., Costreie, M., Watanabe, M., and Todd, A. J.
College/School:College of Medical Veterinary and Life Sciences > School of Psychology & Neuroscience
Journal Name:Neuroscience
Publisher:Elsevier
ISSN:0306-4522
ISSN (Online):1873-7544
Published Online:04 July 2020
Copyright Holders:Copyright © 2020 The Authors
First Published:First published in Neuroscience 450: 113-125
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/ZNP - Centre for Neuroscience
172232The role of NPY-containing inhibitory interneurons in spinal pain pathwaysAndrew ToddBiotechnology and Biological Sciences Research Council (BBSRC)BB/N006119/1NP - Centre for Neuroscience
302893Neuronal circuits for itch in the spinal dorsal hornAndrew ToddMedical Research Council (MRC)MR/S002987/1NP - Centre for Neuroscience