Show simple item record

Files in this item

Thumbnail

Item metadata

dc.contributor.authorSharples, Simon A.
dc.contributor.authorBurma, Nicole E.
dc.contributor.authorBorowska-Fielding, Joanna
dc.contributor.authorKwok, Charlie H. T.
dc.contributor.authorEaton, Shane E. A.
dc.contributor.authorBaker, Glen B.
dc.contributor.authorJean-Xavier, Celine
dc.contributor.authorZhang, Ying
dc.contributor.authorTrang, Tuan
dc.contributor.authorWhelan, Patrick J.
dc.date.accessioned2020-10-06T14:30:03Z
dc.date.available2020-10-06T14:30:03Z
dc.date.issued2020-10-02
dc.identifier.citationSharples , S A , Burma , N E , Borowska-Fielding , J , Kwok , C H T , Eaton , S E A , Baker , G B , Jean-Xavier , C , Zhang , Y , Trang , T & Whelan , P J 2020 , ' A dynamic role for dopamine receptors in the control of mammalian spinal networks ' , Scientific Reports , vol. 10 , 16429 . https://doi.org/10.1038/s41598-020-73230-wen
dc.identifier.issn2045-2322
dc.identifier.otherPURE: 270575656
dc.identifier.otherPURE UUID: bcfa62c6-5ba4-4eff-aee2-1dd333568a2b
dc.identifier.otherRIS: urn:7345B131FF3C5A02A6B30267CFBE7CD8
dc.identifier.otherRIS: Sharples2020
dc.identifier.otherORCID: /0000-0003-2316-1504/work/81798025
dc.identifier.otherScopus: 85091839242
dc.identifier.otherWOS: 000577151500024
dc.identifier.urihttp://hdl.handle.net/10023/20730
dc.descriptionAuthors acknowledge studentships from the Natural Sciences and Engineering Research Council of Canada (NSERC-PGS-D: SAS), the Canadian Institute for Health Research (CIHR: NEB), Alberta Innovates—Health Solutions (AIHS: SAS, NEB), Hotchkiss Brain Institute (SAS, NEB) and the Faculty of Veterinary Medicine (CHTK). This research was supported by grants from NSERC (Discovery grant: PJW), CIHR (PJW, YZ) and the VP Research Office and the Faculty of Medicine & Dentistry at the University of Alberta (GBB).en
dc.description.abstractDopamine is well known to regulate movement through the differential control of direct and indirect pathways in the striatum that express D1 and D2 receptors respectively. The spinal cord also expresses all dopamine receptors; however, how the specific receptors regulate spinal network output in mammals is poorly understood. We explore the receptor-specific mechanisms that underlie dopaminergic control of spinal network output of neonatal mice during changes in spinal network excitability. During spontaneous activity, which is a characteristic of developing spinal networks operating in a low excitability state, we found that dopamine is primarily inhibitory. We uncover an excitatory D1-mediated effect of dopamine on motoneurons and network output that also involves co-activation with D2 receptors. Critically, these excitatory actions require higher concentrations of dopamine; however, analysis of dopamine concentrations of neonates indicates that endogenous levels of spinal dopamine are low. Because endogenous levels of spinal dopamine are low, this excitatory dopaminergic pathway is likely physiologically-silent at this stage in development. In contrast, the inhibitory effect of dopamine, at low physiological concentrations is mediated by parallel activation of D2, D3, D4 and α2 receptors which is reproduced when endogenous dopamine levels are increased by blocking dopamine reuptake and metabolism. We provide evidence in support of dedicated spinal network components that are controlled by excitatory D1 and inhibitory D2 receptors that is reminiscent of the classic dopaminergic indirect and direct pathway within the striatum. These results indicate that network state is an important factor that dictates receptor-specific and therefore dose-dependent control of neuromodulators on spinal network output and advances our understanding of how neuromodulators regulate neural networks under dynamically changing excitability.
dc.format.extent23
dc.language.isoeng
dc.relation.ispartofScientific Reportsen
dc.rightsCopyright © The Author(s) 2020. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.en
dc.subjectRC0321 Neuroscience. Biological psychiatry. Neuropsychiatryen
dc.subjectDASen
dc.subject.lccRC0321en
dc.titleA dynamic role for dopamine receptors in the control of mammalian spinal networksen
dc.typeJournal articleen
dc.description.versionPublisher PDFen
dc.contributor.institutionUniversity of St Andrews.School of Psychology and Neuroscienceen
dc.identifier.doihttps://doi.org/10.1038/s41598-020-73230-w
dc.description.statusPeer revieweden


This item appears in the following Collection(s)

Show simple item record