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dc.contributor.authorFoster, Joshua David
dc.contributor.authorDunford, Catherine
dc.contributor.authorSillar, Keith Thomas
dc.contributor.authorMiles, Gareth Brian
dc.identifier.citationFoster , J D , Dunford , C , Sillar , K T & Miles , G B 2014 , ' Nitric oxide-mediated modulation of the murine locomotor network ' , Journal of Neurophysiology , vol. 111 , no. 3 , pp. 659-674 .
dc.identifier.otherORCID: /0000-0002-8624-4625/work/29135006
dc.identifier.otherORCID: /0000-0003-0171-3814/work/64393764
dc.descriptionCD was supported by a BBSRC studentshipen
dc.description.abstractSpinal motor control networks are regulated by neuromodulatory systems to allow adaptability of movements. The present study aimed to elucidate the role of nitric oxide (NO) in the modulation of mammalian spinal locomotor networks. This was investigated with isolated spinal cord preparations from neonatal mice in which rhythmic locomotor-related activity was induced pharmacologically. Bath application of the NO donor diethylamine NONOate (DEA/NO) decreased the frequency and modulated the amplitude of locomotor-related activity recorded from ventral roots. Removal of endogenous NO with coapplication of a NO scavenger (PTIO) and a nitric oxide synthase (NOS) blocker [nitro-l-arginine methyl ester (l-NAME)] increased the frequency and decreased the amplitude of locomotor-related activity. This demonstrates that endogenously derived NO can modulate both the timing and intensity of locomotor-related activity. The effects of DEA/NO were mimicked by the cGMP analog 8-bromo-cGMP. In addition, the soluble guanylyl cyclase (sGC) inhibitor ODQ blocked the effects of DEA/NO on burst amplitude and frequency, although the frequency effect was only blocked at low concentrations of DEA/NO. This suggests that NO-mediated modulation involves cGMP-dependent pathways. Sources of NO were studied within the lumbar spinal cord during postnatal development (postnatal days 1-12) with NADPH-diaphorase staining. NOS-positive cells in the ventral horn exhibited a rostrocaudal gradient, with more cells in rostral segments. The number of NOS-positive cells was also found to increase during postnatal development. In summary, we have shown that NO, derived from sources within the mammalian spinal cord, modulates the output of spinal motor networks and is therefore likely to contribute to the fine-tuning of locomotor behavior.
dc.relation.ispartofJournal of Neurophysiologyen
dc.subjectSpinal corden
dc.subjectCentral pattern generatoren
dc.subjectMotor controlen
dc.subjectRC0321 Neuroscience. Biological psychiatry. Neuropsychiatryen
dc.titleNitric oxide-mediated modulation of the murine locomotor networken
dc.typeJournal articleen
dc.contributor.sponsorThe Wellcome Trusten
dc.contributor.institutionUniversity of St Andrews. School of Psychology and Neuroscienceen
dc.contributor.institutionUniversity of St Andrews. Institute of Behavioural and Neural Sciencesen
dc.description.statusPeer revieweden

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