Neural circuit synaptic connectivities (the connectome) provide the anatomical foundation for our understanding of nematode nervous system function. However, other non-synaptic routes of communication are known in invertebrates including extrasynaptic volume transmission (EVT), which enables short- and/or long-range communication in the absence of synaptic connections. Although EVT has been highlighted as a facet of Caenorhabditis elegans neurosignaling, no experimental evidence identifies body cavity fluid (pseudocoelomic fluid; PCF) as a vehicle for either neuropeptide or biogenic amine transmission. In the parasitic nematode Ascaris suum FMRFamide-like peptides encoded on flp-18 potently stimulate female reproductive organs but are only expressed in cells that are anatomically distant from the reproductive organ, with no known synaptic connections to this tissue. Here we report a new non-synaptic mode of signaling in nematodes mediated by neuropeptides within the PCF. Our data show that: (i) A. suum PCF (As-PCF) contains a catalogue of neuropeptides including FMRFamide-like peptides and neuropeptide-like proteins; (ii) the A. suum FMRFamide-like peptide As-FLP-18A dominates the As-PCF peptidome; (iii) As-PCF potently modulates nematode reproductive muscle function ex vivo, mirroring the effects of synthetic FLP-18 peptides; (iv) As-PCF activates the C. elegans FLP-18 receptors NPR-4 and -5; (v) As-PCF alters C. elegans behavior and, (vi) FLP-18 and FLP-18 receptors display pan-phylum distribution in nematodes. Here we provide the first direct experimental evidence that supports an extrasynaptic volume route for neuropeptide transmission in nematodes. These data demonstrate non-synaptic signaling within the nematode functional connectome and are pertinent to receptor deorphanisation approaches underpinning drug discovery programs for nematode pathogens.

中文翻译：

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突触外体积传递：线虫中神经肽信号传导的新途径

神经回路突触连接（连接组）为我们对线虫神经系统功能的了解提供了解剖学基础。但是，在无脊椎动物中，其他的非突触通信路径也是已知的，包括突触外体积传输（EVT），它可以在没有突触连接的情况下进行短距离和/或远程通信。尽管EVT已被认为是秀丽隐杆线虫神经信号的一个方面，但尚无实验证据表明体液（伪腔体液； PCF）可作为神经肽或生物胺传递的媒介。在寄生线虫A虫中，在flp-18上编码的FMRFamide样肽可有效刺激女性生殖器官，但仅在解剖上与生殖器官相距较远的细胞中表达，与该组织没有已知的突触连接。在这里，我们报告由PCF内的神经肽介导的线虫中一种新的非突触信号传导模式。我们的数据显示：（i）A. suum PCF（As-PCF）包含一类神经肽，包括FMRFamide样肽和神经肽样蛋白。（ii）A.suum FMRFamide样肽As-FLP-18A支配As-PCF肽组；（iii）As-PCF能够有效地调节离体线虫的生殖肌肉功能，反映出合成的FLP-18肽的作用；（iv）As-PCF激活秀丽隐杆线虫FLP-18受体NPR-4和-5；（v）As-PCF改变秀丽隐杆线虫的行为，并且（vi）FLP-18和FLP-18受体在线虫中显示泛门分布。在这里，我们提供了第一个直接的实验证据，支持线虫中神经肽传递的突触外体积途径。