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

Mechanisms underlying the endogenous dopaminergic inhibition of spinal locomotor circuit function in Xenopus tadpoles.
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DOI:
10.1038/srep35749
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发表时间:
2016-10-20
期刊:
影响因子:
4.6
通讯作者:
Sillar KT
Sillar KT
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Picton LD;Sillar KT

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多巴胺在运动控制电路的发育和调节中起着重要作用。在这里,我们展示了多巴胺对控制非洲爪哇胚胎后蝌蚪运动游泳的中央模式产生电路产生了强有力的影响。多巴胺(0.5-100 μM)可减少假想游泳的发生,并使自发和诱发发作变短、变慢和变弱。D2受体激动剂奎匹罗模仿了这种对游泳的抑制作用,而D4受体拮抗剂L745,870则具有相反的作用。多巴胺再摄取抑制剂安非他酮有效地抑制了假想游泳,证明了多巴胺构成了一个内源性的调节系统。多巴胺和喹比罗也抑制了棘化制剂中的游泳,这表明多巴胺受体位于棘突位置。多巴胺和喹比罗超极化识别节律活跃的脊髓神经元,在游泳和对电流注射的反应中增加流变基和降低尖峰概率。这种超极化是TTX抗性的,并伴随着输入阻力的降低,这表明多巴胺打开了一个K+通道。钾通道阻滞剂氯化钡(但不包括TEA、格列本脲或Tertiapin-Q)显著阻断了这种超极化。总体而言,我们发现内源性释放的多巴胺作用于位于脊髓位置的D2样受体,导致通过开放K+通道快速抑制游泳的调制。
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.
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