Neuropeptides encoded bynlp-49modulate locomotion, arousal and egg-laying behaviours inCaenorhabditis elegansvia the receptor SEB-3

Abstract

Neuropeptide signalling has been implicated in a wide variety of biological processes in diverse organisms, from invertebrates to humans. The Caenorhabditis elegans genome has at least 154 neuropeptide precursor genes, encoding over 300 bioactive peptides. These neuromodulators are thought to largely signal beyond ‘wired’ chemical/electrical synapse connections, therefore creating a ‘wireless’ network for neuronal communication. Here, we investigated how behavioural states are affected by neuropeptide signalling through the G protein-coupled receptor SEB-3, which belongs to a bilaterian family of orphan secretin receptors. Using reverse pharmacology, we identified the neuropeptide NLP-49 as a ligand of this evolutionarily conserved neuropeptide receptor. Our findings demonstrate novel roles for NLP-49 and SEB-3 in locomotion, arousal and egg-laying. Specifically, high-content analysis of locomotor behaviour indicates that seb-3 and nlp-49 deletion mutants cause remarkably similar abnormalities in movement dynamics, which are reversed by overexpression of wild-type transgenes. Overexpression of NLP-49 in AVK interneurons leads to heightened locomotor arousal, an effect that is dependent on seb-3. Finally, seb-3 and nlp-49 mutants also show constitutive egg-laying in liquid medium and alter the temporal pattern of egg-laying in similar ways. Together, these results provide in vivo evidence that NLP-49 peptides act through SEB-3 to modulate behaviour, and highlight the importance of neuropeptide signalling in the control of behavioural states.This article is part of a discussion meeting issue ‘Connectome to behaviour: modelling C. elegans at cellular resolution’.

Food Sensation Modulates Locomotion by Dopamine and Neuropeptide Signaling in a Distributed Neuronal Network

“…Another highly abundant AVK transcript is nlp-49, encoding two neuropeptide-like sequences. Recent work detected NLP-49 effects on arousal and locomotion in ways that would oppose the effects of FLP-1 (Chew et al, 2018). Whether AVK inhibition affects NLP-49 signals, and whether NLP-49 and FLP-1 are used in different contexts or network states, will have to be clarified by future work.…”

Presynaptic Gαo(GOA-1) signals to depress command neuron excitability and allow stretch-dependent modulation of egg laying inCaenorhabditis elegans

“…To understand how Gαo signaling controls the normal two-state pattern of egg laying, we 185 made long-term recordings of adults as they transitioned into and out of the active states in which 186 clusters of several eggs are typically laid. Intervals between egg-laying events were operationally 187 classified into two categories: intra-cluster intervals and inter-cluster intervals, as previously 188 described (Waggoner et al, 1998;Collins and Koelle, 2013;Banerjee et al, 2017;Zang et al, 189 2017;Chew et al, 2018). Intra-cluster intervals (< 4 minutes) are intervals between consecutive 190 egg laying events within a single active state.…”

Combining single-cell RNA-sequencing with a molecular atlas unveils new markers for Caenorhabditis elegans neuron classes

“…( B ) The fold change comparison highlights the genes co-enriched in cluster 14 and in AVK bulk sequencing profile. The expression of nlp-49 and flp-1 mRNA in AVK were previously described (purple) ( 12 , 48 ). Several new potential AVK markers are highlighted in red, including twk-47 .…”