A combined electrophysiological and morphological study of NPY-expressing inhibitory interneurons in the spinal dorsal horn of the mouse

Iwagaki, N., Ganley, R. P., Dickie, A., Polgár, E., Hughes, D. I., Del Rio, P., Revina, Y., Watanabe, M., Todd, A. J. and Riddell, J. S. (2016) A combined electrophysiological and morphological study of NPY-expressing inhibitory interneurons in the spinal dorsal horn of the mouse. Pain, 157(3), pp. 598-612. (doi:10.1097/j.pain.0000000000000407) (PMID:26882346) (PMCID:PMC4751741)

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Abstract

The spinal dorsal horn contains numerous inhibitory interneurons that control transmission of somatosensory information. Although these cells have important roles in modulating pain, we still have limited information about how they are incorporated into neuronal circuits, and this is partly due to difficulty in assigning them to functional populations. Around 15% of inhibitory interneurons in laminae I-III express neuropeptide Y (NPY), but little is known about this population. We therefore used a combined electophysiological/morphological approach to investigate these cells in mice that express green fluorescent protein (GFP) under control of the NPY promoter. We show that GFP is largely restricted to NPY-immunoreactive cells, although it is only expressed by a third of those in lamina I-II. Reconstructions of recorded neurons revealed that they were morphologically heterogeneous, but never islet cells. Many NPY-GFP cells (including cells in lamina III) appeared to be innervated by TRPV1-lacking C fibres, and consistent with this, we found that some lamina III NPY-immunoreactive cells were activated by mechanical noxious stimuli. Projection neurons in lamina III are densely innervated by NPY-containing axons. Our results suggest that this input originates from a small subset of NPY-expressing interneurons, with the projection cells representing only a minority of their output. Taken together with results of previous studies, our findings indicate that somatodendritic morphology is of limited value in classifying functional populations among inhibitory interneurons in the dorsal horn. Since many NPY-expressing cells respond to noxious stimuli, these are likely to have a role in attenuating pain and limiting its spread.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Del Rio, Dr Patricia and Hughes, Dr David I and Iwagaki, Mr Noboru and Riddell, Dr John and Beresford-Polgar, Dr Erika and Dickie, Dr Allen and Todd, Professor Andrew
Authors: Iwagaki, N., Ganley, R. P., Dickie, A., Polgár, E., Hughes, D. I., Del Rio, P., Revina, Y., Watanabe, M., Todd, A. J., and Riddell, J. S.
College/School:College of Medical Veterinary and Life Sciences > Institute of Neuroscience and Psychology
Journal Name:Pain
Publisher:Lippincott Williams & Wilkins
ISSN:0304-3959
ISSN (Online):1872-6623
Copyright Holders:Copyright © 2015 The Authors
First Published:First published in Pain 157(3):598-612
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
571071Modulating 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/J000620/1RI NEUROSCIENCE & PSYCHOLOGY
644161Defining pain circuitry in health and diseaseAndrew ToddWellcome Trust (WELLCOME)102645/Z/13/ZINP - CENTRE FOR NEUROSCIENCE
569571Populations of inhibitory interneurons in the superficial dorsal horn of the spinal cord.Andrew ToddBiotechnology and Biological Sciences Research Council (BBSRC)BB/J0001082/1RI NEUROSCIENCE & PSYCHOLOGY