Year: 2020
Type: preprint
Abstract: 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.
Language: English
Subfield: Cellular and Molecular Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: green
Funders: Department of Agriculture, Environment and Rural Affairs, UK Government, Fonds Wetenschappelijk Onderzoek, Vlaamse regering, National Institutes of Health, Directorate for Biological Sciences, Biotechnology and Biological Sciences Research Council, National Institute of General Medical Sciences, National Institute of Diabetes and Digestive and Kidney Diseases, National Center for Research Resources
Awards: Acquisition of a High-Field Dual Source FTICR-MS for Pharmaceutical Research, Functional deciphering of TRH- and thyrostimulin-related signaling in growth regulation, G5175589797, G6987338415, Mass Spectrometric Studies of Neuropeptides in Feeding, EVOLUTION OF THE NEMATODE INTESTINE, A KEY HOST INTERFACE
OpenAlex ID: W3048023272