Heteromeric α/β glycine receptors regulate excitability in parvalbumin-expressing dorsal horn neurons through phasic and tonic glycinergic inhibition

Gradwell, M.A., Boyle, K.A., Callister, R.J., Hughes, D.I. and Graham, B.A. (2017) Heteromeric α/β glycine receptors regulate excitability in parvalbumin-expressing dorsal horn neurons through phasic and tonic glycinergic inhibition. Journal of Physiology, 595(23), pp. 7185-7202. (doi: 10.1113/JP274926) (PMID:28905384) (PMCID:PMC5709328)

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Abstract

The dorsal horn (DH) of the spinal cord is an important site for modality specific processing of sensory information and is essential for contextually relevant sensory experience. Parvalbumin-expressing inhibitory interneurons (PV + INs) have functional properties and connectivity that enables them to segregate tactile and nociceptive information. Here we examine inhibitory drive to PV + INs using targeted patch-clamp recording in spinal cord slices from adult transgenic mice that express enhanced green fluorescent protein in PV + INs. Analysis of inhibitory synaptic currents showed glycinergic transmission is the dominant form of phasic inhibition to PV + INs. In addition, PV + INs expressed robust glycine-mediated tonic currents, however, we found no evidence for tonic GABAergic currents. Manipulation of extracellular glycine by blocking either, or both, the glial and neuronal glycine transporters markedly decreased PV + IN excitability, as assessed by action potential discharge. This decreased excitability was replicated when tonic glycinergic currents were increased by electrically activating glycinergic synapses. Finally, we show that both phasic and tonic forms of glycinergic inhibition are mediated by heteromeric α/β glycine receptors. This differs from GABAA receptors in the dorsal horn, where different receptor stoichiometries underlie phasic and tonic inhibition. Together these data suggest both phasic and tonic glycinergic inhibition regulate the output of PV + INs and contribute to the processing and segregation of tactile and nociceptive information. The shared stoichiometry for phasic and tonic glycine receptors suggests pharmacology is unlikely to be able to selectively target each form of inhibition in PV + INs.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Boyle, Dr Kieran and Hughes, Dr David I
Authors: Gradwell, M.A., Boyle, K.A., Callister, R.J., Hughes, D.I., and Graham, B.A.
College/School:College of Medical Veterinary and Life Sciences > Institute of Neuroscience and Psychology
Journal Name:Journal of Physiology
Publisher:Wiley
ISSN:0022-3751
ISSN (Online):1469-7793
Published Online:14 September 2017
Copyright Holders:Copyright © 2017 The Authors
First Published:First published in Journal of Physiology 595(23): 7185-7202
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