Signaling via the FLP-14/FRPR-19 neuropeptide pathway sustains nociceptive response to repeated noxious stimuli in C. elegans

• DOI: 10.1371/journal.pgen.1009880
• Publication Date: 2021-11-08T18:41:30Z
• Authors: Filipe Marques; Laurent Falquet; Elke Vandewyer; Isabel Beets; Dominique A. Glauser
• Keywords: Nociceptor

In order to thrive in constantly changing environments, animals must adaptively respond threatening events. Noxious stimuli are not only processed according their absolute intensity, but also context. Adaptation processes can cause habituate at different rates and degrees response permanent or repeated stimuli. Here, we used a forward genetic approach Caenorhabditis elegans identify neuropeptidergic pathway, essential prevent fast habituation maintain robust withdrawal responses noxious This pathway involves the FRPR-19A FRPR-19B G-protein coupled receptor isoforms produced from frpr-19 gene by alternative splicing. Loss overexpression of each both impair caused optogenetic activation polymodal FLP nociceptor neuron. Furthermore, identified FLP-8 FLP-14 as FRPR-19 ligands vitro . flp-14 , flp-8 was promote is part same vivo Expression cell-specific rescue analyses suggest that acts nociceptive neurons downstream interneurons, whereas interneurons. Importantly, impairment FLP-14/FRPR-19 accelerated FLP-specific activation, well heat harsh touch Collectively, our data well-adjusted neuromodulation via contributes signals C counteracts otherwise tend rapidly reduce aversive