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dc.contributor.authorNascimento, Filipe
dc.contributor.authorBroadhead, Matthew James
dc.contributor.authorTetringa, Efstathia
dc.contributor.authorTsape, Eirini
dc.contributor.authorZagoraiou, Laskaro
dc.contributor.authorMiles, Gareth Brian
dc.date.accessioned2020-03-10T17:30:03Z
dc.date.available2020-03-10T17:30:03Z
dc.date.issued2020-03-09
dc.identifier266483367
dc.identifier3daee16f-c5a8-4e88-88ed-44c4af972939
dc.identifier85081944744
dc.identifier000519713500001
dc.identifier.citationNascimento , F , Broadhead , M J , Tetringa , E , Tsape , E , Zagoraiou , L & Miles , G B 2020 , ' Synaptic mechanisms underlying modulation of locomotor-related motoneuron output by premotor cholinergic interneurons ' , eLife , vol. 9 , e54170 . https://doi.org/10.7554/eLife.54170en
dc.identifier.issn2050-084X
dc.identifier.otherORCID: /0000-0002-8624-4625/work/70618975
dc.identifier.urihttps://hdl.handle.net/10023/19633
dc.descriptionF Nascimento was supported by The Alfred Dunhill Links Foundation. G B Miles and M J Broadhead received support from Biotechnology and Biological Sciences Research Council Grant BB/M021793/1. L Zagoraiou and E Tsape were supported by Fondation Santé.en
dc.description.abstractSpinal motor networks are formed by diverse populations of interneurons that set the strength and rhythmicity of behaviors such as locomotion. A small cluster of cholinergic interneurons, expressing the transcription factor Pitx2, modulates the intensity of muscle activation via ‘C-bouton’ inputs to motoneurons. However, the synaptic mechanisms underlying this neuromodulation remain unclear. Here, we confirm in mice that Pitx2+ interneurons are active during fictive locomotion and that their chemogenetic inhibition reduces the amplitude of motor output. Furthermore, after genetic ablation of cholinergic Pitx2+ interneurons, M2 receptor-dependent regulation of the intensity of locomotor output is lost. Conversely, chemogenetic stimulation of Pitx2+ interneurons leads to activation of M2 receptors on motoneurons, regulation of Kv2.1 channels and greater motoneuron output due to an increase in the inter-spike afterhyperpolarization and a reduction in spike half-width. Our findings elucidate synaptic mechanisms by which cholinergic spinal interneurons modulate the final common pathway for motor output.
dc.format.extent26
dc.format.extent3578732
dc.language.isoeng
dc.relation.ispartofeLifeen
dc.subjectRC0321 Neuroscience. Biological psychiatry. Neuropsychiatryen
dc.subjectDASen
dc.subjectBDCen
dc.subjectR2Cen
dc.subject.lccRC0321en
dc.titleSynaptic mechanisms underlying modulation of locomotor-related motoneuron output by premotor cholinergic interneuronsen
dc.typeJournal articleen
dc.contributor.sponsorBBSRCen
dc.contributor.sponsorBBSRCen
dc.contributor.institutionUniversity of St Andrews. School of Psychology and Neuroscienceen
dc.contributor.institutionUniversity of St Andrews. Centre for Biophotonicsen
dc.contributor.institutionUniversity of St Andrews. Institute of Behavioural and Neural Sciencesen
dc.identifier.doi10.7554/eLife.54170
dc.description.statusPeer revieweden
dc.identifier.grantnumberBB/M021793/1en
dc.identifier.grantnumberBB/E019803/1en


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