An Afferent Neuropeptide System Transmits Mechanosensory Signals Triggering Sensitization and Arousal in C. elegans

Yee Lian Chew, Yoshinori Tanizawa, Yongmin Cho, Buyun Zhao, Alex J. Yu, Evan L. Ardiel, Ithai Rabinowitch, Jihong Bai, Catharine H. Rankin, Hang Lu, Isabel Beets, William R. Schafer*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

31 Scopus citations


Sensitization is a simple form of behavioral plasticity by which an initial stimulus, often signaling danger, leads to increased responsiveness to subsequent stimuli. Cross-modal sensitization is an important feature of arousal in many organisms, yet its molecular and neural mechanisms are incompletely understood. Here we show that in C. elegans, aversive mechanical stimuli lead to both enhanced locomotor activity and sensitization of aversive chemosensory pathways. Both locomotor arousal and cross-modal sensitization depend on the release of FLP-20 neuropeptides from primary mechanosensory neurons and on their receptor FRPR-3. Surprisingly, the critical site of action of FRPR-3 for both sensory and locomotor arousal is RID, a single neuroendocrine cell specialized for the release of neuropeptides that responds to mechanical stimuli in a FLP-20-dependent manner. Thus, FLP-20 peptides function as an afferent arousal signal that conveys mechanosensory information to central neurons that modulate arousal and other behavioral states. Video Abstract:[Figure presented] Arousal is an important conserved behavioral state where animals show increased sensory responsiveness and locomotor hyperactivity. Chew et al. identify a neuromodulatory pathway that enables mechanosensory neurons to promote both sensory and locomotor arousal via activation of a neuroendocrine center.

Original languageAmerican English
Pages (from-to)1233-1246.e6
Issue number6
StatePublished - 19 Sep 2018

Bibliographical note

Funding Information:
The authors gratefully acknowledge Denise Walker for critical reading of the manuscript, and members of the Schafer, de Bono, and Taylor labs (MRC LMB) and Young-Jai You (Nagoya University) for helpful discussions. We sincerely thank Inja Radman for some DNA constructs. Some strains were provided by the CGC, which is funded by the National Institutes of Health (NIH P40 OD010440 ). We are grateful to Dr. Mei Zhen for the RID::Chrimson line ZM9315. This work was funded by grants from the Medical Research Council ( MC-A023-5PB91 ) and the Wellcome Trust ( WT103784MA ) to W.R.S., from the NIH ( R21DC015652 ) to W.R.S. and H.L., from the NIH ( R01NS096581 and R01GM088333 ) to H.L., from the Natural Sciences and Engineering Research Council of Canada (NSERC grant #122216-2013 ) to C.H.R., and from the NIH ( R21DC016258 ) to J.B. Y.L.C. is funded by an EMBO Long-term Fellowship (ALTF 403-2016). A.J.Y. is funded by a NSERC Canada Graduate Scholarship-Master’s (CGS-M). E.L.A. is funded by a NSERC CGS. I.B. is funded by an EMBO Long-term Fellowship (ALTF 387-2015) and is a fellow of the Research Foundation - Flanders (FWO).

Publisher Copyright:
© 2018 MRC Laboratory of Molecular Biology


  • C. elegans
  • arousal
  • behavioral states
  • neuropeptides
  • sensitization


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