Neurobiology Division, MRC Laboratory of Molecular Biology, Cambridge CB2 0QH, UK.
MRC London Institute of Medical Sciences, London W12 0NN, UK.
Philos Trans R Soc Lond B Biol Sci. 2018 Sep 10;373(1758):20170368. doi: 10.1098/rstb.2017.0368.
Neuropeptide signalling has been implicated in a wide variety of biological processes in diverse organisms, from invertebrates to humans. The genome has at least 154 neuropeptide precursor genes, encoding over 300 bioactive peptides. These neuromodulators are thought to largely signal beyond 'wired' chemical/electrical synapse connections, therefore creating a 'wireless' network for neuronal communication. Here, we investigated how behavioural states are affected by neuropeptide signalling through the G protein-coupled receptor SEB-3, which belongs to a bilaterian family of orphan secretin receptors. Using reverse pharmacology, we identified the neuropeptide NLP-49 as a ligand of this evolutionarily conserved neuropeptide receptor. Our findings demonstrate novel roles for NLP-49 and SEB-3 in locomotion, arousal and egg-laying. Specifically, high-content analysis of locomotor behaviour indicates that and deletion mutants cause remarkably similar abnormalities in movement dynamics, which are reversed by overexpression of wild-type transgenes. Overexpression of NLP-49 in AVK interneurons leads to heightened locomotor arousal, an effect that is dependent on Finally, and mutants also show constitutive egg-laying in liquid medium and alter the temporal pattern of egg-laying in similar ways. Together, these results provide evidence that NLP-49 peptides act through SEB-3 to modulate behaviour, and highlight the importance of neuropeptide signalling in the control of behavioural states.This article is part of a discussion meeting issue 'Connectome to behaviour: modelling at cellular resolution'.
神经肽信号在从无脊椎动物到人类等各种生物的各种生物过程中都有涉及。基因组至少有 154 种神经肽前体基因，编码超过 300 种生物活性肽。这些神经调节剂被认为主要在“有线”化学/电突触连接之外传递信号，因此为神经元通讯创建了一个“无线”网络。在这里，我们通过属于双边类孤儿分泌素受体家族的 G 蛋白偶联受体 SEB-3 研究了神经肽信号如何影响行为状态。使用反向药理学，我们确定了神经肽 NLP-49 是这种进化上保守的神经肽受体的配体。我们的研究结果表明 NLP-49 和 SEB-3 在运动、觉醒和产卵中具有新的作用。具体而言，对运动行为的高内涵分析表明，和缺失突变体在运动动力学方面引起了非常相似的异常，而野生型转基因的过表达则逆转了这些异常。在 AVK 中间神经元中过表达 NLP-49 会导致运动觉醒增加，这种作用依赖于。此外，和突变体也在液体培养基中表现出持续产卵，并以类似的方式改变产卵的时间模式。总之，这些结果提供了证据表明 NLP-49 肽通过 SEB-3 来调节行为，并强调了神经肽信号在行为状态控制中的重要性。本文是“从细胞分辨率到行为的连接组：建模”讨论会议的一部分。
