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Mechanisms underlying the endogenous dopaminergic inhibition of spinal locomotor circuit function in Xenopus tadpoles

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Sillar_2016_SciRep_Mechanisms_CCBY_FinalPublishedVersion.pdf (10.48Mb)
Date
20/10/2016
Author
Picton, Laurence David
Sillar, Keith Thomas
Keywords
RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
NDAS
BDC
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Abstract
Dopamine plays important roles in the development and modulation of motor control circuits. Here we show that dopamine exerts potent effects on the central pattern generator circuit controlling locomotory swimming in post-embryonic Xenopus tadpoles. Dopamine (0.5–100 μM) reduced fictive swim bout occurrence and caused both spontaneous and evoked episodes to become shorter, slower and weaker. The D2-like receptor agonist quinpirole mimicked this repertoire of inhibitory effects on swimming, whilst the D4 receptor antagonist, L745,870, had the opposite effects. The dopamine reuptake inhibitor bupropion potently inhibited fictive swimming, demonstrating that dopamine constitutes an endogenous modulatory system. Both dopamine and quinpirole also inhibited swimming in spinalised preparations, suggesting spinally located dopamine receptors. Dopamine and quinpirole hyperpolarised identified rhythmically active spinal neurons, increased rheobase and reduced spike probability both during swimming and in response to current injection. The hyperpolarisation was TTX-resistant and was accompanied by decreased input resistance, suggesting that dopamine opens a K+ channel. The K+ channel blocker barium chloride (but not TEA, glybenclamide or tertiapin-Q) significantly occluded the hyperpolarisation. Overall, we show that endogenously released dopamine acts upon spinally located D2-like receptors, leading to a rapid inhibitory modulation of swimming via the opening of a K+ channel.
Citation
Picton , L D & Sillar , K T 2016 , ' Mechanisms underlying the endogenous dopaminergic inhibition of spinal locomotor circuit function in Xenopus tadpoles ' , Scientific Reports , vol. 6 , 35749 . https://doi.org/10.1038/srep35749
Publication
Scientific Reports
Status
Peer reviewed
DOI
https://doi.org/10.1038/srep35749
ISSN
2045-2322
Type
Journal article
Rights
Copyright 2016 the Authors. This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
Description
This work was supported by the Biotechnology and Biological Science Research Council (BBSRC) [grant number BB/J01446X/1].
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  • University of St Andrews Research
URI
http://hdl.handle.net/10023/9714

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