Distinct forms of synaptic inhibition and neuromodulation regulate calretinin positive neuron excitability in the spinal cord dorsal horn

Smith, K.M., Boyle, K.A., Mustapa, M., Jobling, P., Callister, R.J., Hughes, D.I. and Graham, B.A. (2016) Distinct forms of synaptic inhibition and neuromodulation regulate calretinin positive neuron excitability in the spinal cord dorsal horn. Neuroscience, 326, pp. 10-21. (doi:10.1016/j.neuroscience.2016.03.058) (PMID:27045594) (PMCID:PMC4919388)

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Abstract

The dorsal horn (DH) of the spinal cord contains a heterogenous population of neurons that process incoming sensory signals before information ascends to the brain. We have recently characterized calretinin-expressing (CR+) neurons in the DH and shown that they can be divided into excitatory and inhibitory subpopulations. The excitatory population receives high-frequency excitatory synaptic input and expresses delayed firing action potential discharge, whereas the inhibitory population receives weak excitatory drive and exhibits tonic or initial bursting discharge. Here, we characterize inhibitory synaptic input and neuromodulation in the two CR+ populations, in order to determine how each is regulated. We show that excitatory CR+ neurons receive mixed inhibition from GABAergic and glycinergic sources, whereas inhibitory CR+ neurons receive inhibition, which is dominated by glycine. Noradrenaline and serotonin produced robust outward currents in excitatory CR+ neurons, predicting an inhibitory action on these neurons, but neither neuromodulator produced a response in CR+ inhibitory neurons. In contrast, enkephalin (along with selective mu and delta opioid receptor agonists) produced outward currents in inhibitory CR+ neurons, consistent with an inhibitory action but did not affect the excitatory CR+ population. Our findings show that the pharmacology of inhibitory inputs and neuromodulator actions on CR+ cells, along with their excitatory inputs can define these two subpopulations further, and this could be exploited to modulate discrete aspects of sensory processing selectively in the DH.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Boyle, Dr Kieran and Hughes, Dr David I
Authors: Smith, K.M., Boyle, K.A., Mustapa, M., Jobling, P., 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:Neuroscience
Publisher:Elsevier
ISSN:0306-4522
ISSN (Online):1873-7544
Published Online:01 April 2016
Copyright Holders:Copyright © 2016 The Authors
First Published:First published in Neuroscience 326: 10-21
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