School of Psychology and Neuroscience, University of St Andrews, St Andrews, United Kingdom.
J Neurophysiol. 2022 Apr 1;127(4):1098-1116. doi: 10.1152/jn.00106.2021. Epub 2022 Mar 16.
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 larvae. We measured fictive motor patterns in isolated CNS preparations, using a combination of Ca 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 Ca 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. Using a combination of pharmacology, electrophysiology, and Ca imaging, we find that signaling through mACh receptors plays a critical role in rhythmogenesis in different regions of the 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.
在控制四肢动物在地形上运动的运动系统中，对节律产生的机制进行了广泛的研究；然而，对于软体陆地动物的节律产生知之甚少。在这里，我们探索了在软体幼虫的中枢神经系统 (CNS) 中，毒蕈碱型乙酰胆碱受体 (mAChR) 调节的节律产生网络是如何分布的。我们使用钙成像和电生理学相结合的方法，在离体 CNS 标本中测量虚构的运动模式，同时通过药理学手段操纵 mAChR 信号。mAChR 激动剂 oxotremorine 的浴应用增强了前胸部的双侧不对称活动，并促进了后腹部的爆发。mAChR 拮抗剂东莨菪碱的应用抑制了这些区域的节律产生，并阻断了 oxotremorine 的作用。Oxotremorine 在没有脑叶的制剂中触发虚构的向前爬行。Oxotremorine 还增强了分离的后腹部 CNS 节段以及分离的前脑和胸部区域的节律性活动，但它不会在前腹部节段诱导节律性活动。东莨菪碱浴应用于减少的制剂降低基线 Ca 水平并消除节律性活动。总的来说，这些结果表明 mAChR 信号在幼虫 CNS 的多个部位产生节律中起作用。这项工作进一步了解了软体运动中的运动控制，并为在新兴的遗传上可操作的运动系统中研究节律产生网络提供了基础。我们使用药理学、电生理学和钙成像的组合，发现 mACh 受体信号在幼虫 CNS 的不同区域的节律产生中起着关键作用。mAChR 依赖性节律发生器存在于幼虫 CNS 的远端区域，为头部摆动行为和向前运动的中枢模式产生网络 (CPG) 提供了功能底物。这为在穿越地形的软体动物中运动 CPG 的运作提供了新的见解。
