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dc.contributor.authorPicton, Laurence David
dc.contributor.authorNascimento, Filipe
dc.contributor.authorBroadhead, Matthew James
dc.contributor.authorSillar, Keith Thomas
dc.contributor.authorMiles, Gareth Brian
dc.identifier.citationPicton , L D , Nascimento , F , Broadhead , M J , Sillar , K T & Miles , G B 2017 , ' Sodium pumps mediate activity-dependent changes in mammalian motor networks ' , Journal of Neuroscience , vol. 37 , no. 4 , pp. 906-921 .
dc.identifier.otherPURE: 248183781
dc.identifier.otherPURE UUID: c83ca744-02f7-4e5a-844c-fdc7e497ca1b
dc.identifier.otherPubMed: 28123025
dc.identifier.otherPubMed: 28123025
dc.identifier.otherScopus: 85010901105
dc.identifier.otherORCID: /0000-0002-8624-4625/work/29135001
dc.identifier.otherWOS: 000393569300015
dc.identifier.otherORCID: /0000-0003-0171-3814/work/64393774
dc.descriptionFunding: Laurence Picton [grant number BB/JO1446X/1] and Matthew Broadhead [grant number BB/M021793/1] were supported by the Biotechnology and Biological Science Research Council (BBSRC). Filipe Nascimento was supported by The Alfred Dunhill Links Foundation.en
dc.description.abstractUbiquitously expressed sodium pumps are best known for maintaining the ionic gradients and resting membrane potential required for generating action potentials. However, activity- and state-dependent changes in pump activity can also influence neuronal firing and regulate rhythmic network output. Here we demonstrate that changes in sodium pump activity regulate locomotor networks in the spinal cord of neonatal mice. The sodium pump inhibitor, ouabain, increased the frequency and decreased the amplitude of drug-induced locomotor bursting, effects that were dependent on the presence of the neuromodulator dopamine. Conversely, activating the pump with the sodium ionophore monensin decreased burst frequency. When more "natural" locomotor output was evoked using dorsal-root stimulation, ouabain increased burst frequency and extended locomotor episode duration, whereas monensin slowed and shortened episodes. Decreasing the time between dorsal-root stimulation, and therefore interepisode interval, also shortened and slowed activity, suggesting that pump activity encodes information about past network output and contributes to feedforward control of subsequent locomotor bouts. Using whole-cell patch-clamp recordings from spinal motoneurons and interneurons, we describe a long-duration (∼60 s), activity-dependent, TTX- and ouabain-sensitive, hyperpolarization (∼5 mV), which is mediated by spike-dependent increases in pump activity. The duration of this dynamic pump potential is enhanced by dopamine. Our results therefore reveal sodium pumps as dynamic regulators of mammalian spinal motor networks that can also be affected by neuromodulatory systems. Given the involvement of sodium pumps in movement disorders, such as amyotrophic lateral sclerosis and rapid-onset dystonia parkinsonism, knowledge of their contribution to motor network regulation also has considerable clinical importance.
dc.relation.ispartofJournal of Neuroscienceen
dc.rightsCopyright © 2017 Picton et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License Creative Commons Attribution 4.0 International, which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.en
dc.subjectSodium pumpen
dc.subjectCentral pattern generatoren
dc.subjectSpinal corden
dc.subjectQH301 Biologyen
dc.subjectRC0321 Neuroscience. Biological psychiatry. Neuropsychiatryen
dc.titleSodium pumps mediate activity-dependent changes in mammalian motor networksen
dc.typeJournal articleen
dc.description.versionPublisher PDFen
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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