A conserved behavioral role for a nematode interneuron neuropeptide receptor
Abstract
Neuropeptides are evolutionarily conserved modulators of many aspects of animal behavior and physiology, and expand the repertoire of processes that can be controlled by a limited number of neurons. Deciphering the neuropeptidergic codes that govern distinct processes requires systematic functional analyses of neuropeptides and their cognate receptors. Even in well-studied model organisms like Caenorhabditis elegans, however, such efforts have been precluded by a lack of mutant reagents. Here, we generated and screened 21 C. elegans neuropeptide G-protein coupled receptor mutants with no pre-existing reagents for the touch-evoked escape response, and implicated six receptors expressed in diverse neuron classes representing multiple circuit levels in this behavior. We further characterized the mutant with the most severe phenotype, frpr-14, which was defective in multiple behavioral paradigms. We leveraged this range of phenotypes to reveal that FRPR-14 modulation of different precommand interneuron classes, AVH and AIB, can drive distinct behavioral subsets, demonstrating cellular context-dependent roles for FRPR-14 signaling. We then show that Caenorhabditis briggsae CBR-FRPR-14 modulates an AVH-like interneuron pair to regulate the same behaviors as C. elegans but to a smaller extent. Our results also suggest that differences in touch-evoked escape circuit architecture between closely related species results from changes in neuropeptide receptor expression pattern, as opposed to ligand–receptor pairing. This study provides insights into the principles utilized by a compact, multiplexed nervous system to generate intraspecific behavioral complexity and interspecific variation.
Additional Information
© The Author(s) 2021. Published by Oxford University Press on behalf of Genetics Society of America. This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model). Received: 24 August 2021; Accepted: 28 October 2021; Published: 06 November 2021; Corrected and typeset: 25 November 2021. Some strains were provided by the CGC, which is funded by NIH Office of Research Infrastructure Programs (P40 OD010440). WormBase provided key molecular and genetic information. Some strains were provided by the lab of Dr Shohei Mitani as part of the National Bioresource Project. We thank Shu Fay Ung for generating the schematic in Figure 1A. Conceptualization—C.M.C. and P.W.S. Experimental design and data analysis—C.M.C., W.C., W.W., and X.W. Molecular cloning and transgenesis—C.M.C. Caenorhabditis elegans CRISPR mutagenesis—H.P. Caenorhabditis briggsae CRISPR mutagenesis—S.M.C. Touch-evoked escape response assays—W.C. Motility assays—W.W. Male mating assays—X.W. Microscopy and neuron identification—C.M.C. C.M.C. wrote the paper with input from all coauthors. Funding acquisition—P.W.S. This work was funded by NIH grants R240D023041 and R01NS113119 to P.W.S. Cynthia M. Chai, Wen Chen and Wan-Rong Wong contributed equally to this work. The authors declare that there is no conflict of interest.Attached Files
Supplemental Material - iyab198_supplementary_data.pdf
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Additional details
- PMCID
- PMC8733633
- Eprint ID
- 112240
- DOI
- 10.1093/genetics/iyab198
- Resolver ID
- CaltechAUTHORS:20211206-235720208
- NIH
- P40 OD010440
- NIH
- R240D023041
- NIH
- R01NS113119
- Created
-
2021-12-07Created from EPrint's datestamp field
- Updated
-
2023-07-07Created from EPrint's last_modified field
- Caltech groups
- Division of Biology and Biological Engineering (BBE)