Localization of muscarinic acetylcholine receptor-dependent rhythm-generating modules in the Drosophila larval locomotor network.

Localization of muscarinic acetylcholine receptor-dependent rhythm-generating modules in the Drosophila larval locomotor network.
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毒蕈碱乙酰胆碱受体依赖性节奏模块在果蝇幼虫运动网络中的定位。

DOI:
10.1152/jn.00106.2021
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发表时间:
2022-04-01
影响因子:
2.5
通讯作者:
--
中科院分区:
医学3区
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--
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在控制四肢动物在地形上运动的运动系统中,节律产生的机制已经被广泛研究;然而,我们对陆生软体动物的节律产生知之甚少。本研究探讨了毒蕈碱乙酰胆碱受体(mAChR)调节的节律产生网络在软体果蝇幼虫中枢神经系统(CNS)中的分布。我们在分离的CNS制剂中测量了有效的运动模式,使用Ca2+成像和电生理学的组合,同时在药理学上操纵mAChR信号。mAChR激动剂氧甲氧胺的大量应用增强了胸前区域的双侧不对称活动,并促进了后腹部区域的破裂。应用mAChR拮抗剂东莨菪碱可抑制这些区域的节律产生,并阻断氧tremorine的作用。在没有脑叶的情况下,氧tremorine触发了实际的向前爬行。氧tremorine也增强了孤立的腹后中枢神经系统节段以及孤立的大脑前部和胸部区域的节律性活动,但它没有引起孤立的腹前节段的节律性活动。东莨菪碱浴应用于减少的制剂降低基线Ca2+水平和消除节律性活动。总的来说,这些结果表明,在幼体中枢神经系统的多个部位,mAChR信号在节律产生中起作用。这项工作进一步加深了我们对软体运动中运动控制的理解,并为研究新兴的遗传可调控运动系统中的节律产生网络提供了基础。结合药理学、电生理学和Ca2+成像,我们发现通过mACh受体的信号在果蝇幼虫中枢神经系统不同区域的节律发生中起着关键作用。依赖于machr的节律发生器存在于幼虫中枢神经系统的远端区域,为中枢模式生成网络(cpg)提供功能基础,cpg是头部扫描行为和向前运动的基础。这为在地形上导航的软体动物的运动CPG操作提供了新的见解。
Mechanisms of rhythm generation have been extensively studied in motor systems that control locomotion over terrain in limbed animals; however, much less is known about rhythm generation in soft-bodied terrestrial animals. Here we explored how muscarinic acetylcholine receptor (mAChR)-modulated rhythm-generating networks are distributed in the central nervous system (CNS) of soft-bodied Drosophila larvae. We measured fictive motor patterns in isolated CNS preparations, using a combination of Ca2+ imaging and electrophysiology while manipulating mAChR signaling pharmacologically. Bath application of the mAChR agonist oxotremorine potentiated bilaterally asymmetric activity in anterior thoracic regions and promoted bursting in posterior abdominal regions. Application of the mAChR antagonist scopolamine suppressed rhythm generation in these regions and blocked the effects of oxotremorine. Oxotremorine triggered fictive forward crawling in preparations without brain lobes. Oxotremorine also potentiated rhythmic activity in isolated posterior abdominal CNS segments as well as isolated anterior brain and thoracic regions, but it did not induce rhythmic activity in isolated anterior abdominal segments. Bath application of scopolamine to reduced preparations lowered baseline Ca2+ levels and abolished rhythmic activity. Overall, these results suggest that mAChR signaling plays a role in enabling rhythm generation at multiple sites in the larval CNS. This work furthers our understanding of motor control in soft-bodied locomotion and provides a foundation for study of rhythm-generating networks in an emerging genetically tractable locomotor system. NEW & NOTEWORTHY Using a combination of pharmacology, electrophysiology, and Ca2+ imaging, we find that signaling through mACh receptors plays a critical role in rhythmogenesis in different regions of the Drosophila larval CNS. mAChR-dependent rhythm generators reside in distal regions of the larval CNS and provide functional substrates for central pattern-generating networks (CPGs) underlying headsweep behavior and forward locomotion. This provides new insights into locomotor CPG operation in soft-bodied animals that navigate over terrain.
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