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• W3212859009 endingPage "e1009880" @default.
• W3212859009 startingPage "e1009880" @default.
• W3212859009 abstract "In order to thrive in constantly changing environments, animals must adaptively respond to threatening events. Noxious stimuli are not only processed according to their absolute intensity, but also to their context. Adaptation processes can cause animals to habituate at different rates and degrees in response to permanent or repeated stimuli. Here, we used a forward genetic approach in Caenorhabditis elegans to identify a neuropeptidergic pathway, essential to prevent fast habituation and maintain robust withdrawal responses to repeated noxious stimuli. This pathway involves the FRPR-19A and FRPR-19B G-protein coupled receptor isoforms produced from the frpr-19 gene by alternative splicing. Loss or overexpression of each or both isoforms can impair withdrawal responses caused by the optogenetic activation of the polymodal FLP nociceptor neuron. Furthermore, we identified FLP-8 and FLP-14 as FRPR-19 ligands in vitro. flp-14, but not flp-8, was essential to promote withdrawal response and is part of the same genetic pathway as frpr-19 in vivo. Expression and cell-specific rescue analyses suggest that FRPR-19 acts both in the FLP nociceptive neurons and downstream interneurons, whereas FLP-14 acts from interneurons. Importantly, genetic impairment of the FLP-14/FRPR-19 pathway accelerated the habituation to repeated FLP-specific optogenetic activation, as well as to repeated noxious heat and harsh touch stimuli. Collectively, our data suggest that well-adjusted neuromodulation via the FLP-14/FRPR-19 pathway contributes to promote nociceptive signals in C. elegans and counteracts habituation processes that otherwise tend to rapidly reduce aversive responses to repeated noxious stimuli." @default.
• W3212859009 created "2021-11-22" @default.
• W3212859009 creator A5009886872 @default.
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• W3212859009 creator A5070285020 @default.
• W3212859009 date "2021-11-08" @default.
• W3212859009 modified "2023-10-02" @default.
• W3212859009 title "Signaling via the FLP-14/FRPR-19 neuropeptide pathway sustains nociceptive response to repeated noxious stimuli in C. elegans" @default.
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• W3212859009 doi "https://doi.org/10.1371/journal.pgen.1009880" @default.
• W3212859009 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/8601619" @default.
• W3212859009 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/34748554" @default.
• W3212859009 hasPublicationYear "2021" @default.
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• W3212859009 citedByCount "6" @default.

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