Efforts are ongoing to map synaptic wiring diagrams, or connectomes, understand the neural basis of brain function. However, chemical synapses represent only one type functionally important neuronal connection; in particular, extrasynaptic, "wireless" signaling by neuropeptides is widespread and plays essential roles all nervous systems. By integrating single-cell anatomical gene-expression datasets with biochemical analysis receptor-ligand interactions, we have generated a draft connectome...

Neuropeptides and peptide hormones are ancient, widespread signaling molecules that underpin almost all brain functions. They constitute a broad ligand-receptor network, mainly by binding to G protein-coupled receptors (GPCRs). However, the organization of peptidergic network roles many peptides remain elusive, as our insight into peptide-receptor interactions is limited GPCRs still orphan receptors. Here we report genome-wide peptide-GPCR interaction map in Caenorhabditis elegans. By...

Vasopressin- and oxytocin-related neuropeptides are key regulators of animal physiology, including water balance reproduction. Although these also modulate social behavior cognition in mammals, the mechanism for influencing behavioral plasticity evolutionary origin effects not well understood. Here, we present a functional vasopressin- oxytocin-like signaling system nematode Caenorhabditis elegans. Through activation its receptor NTR-1, vasopressin/oxytocin-related neuropeptide, designated...

Like most organisms, the nematode Caenorhabditis elegans relies heavily on neuropeptidergic signaling. This tiny animal represents a suitable model system to study signaling networks with single cell resolution due availability of powerful molecular and genetic tools. The worm's complete genome sequence allows researchers browse through it, uncovering putative neuropeptides their cognate G protein-coupled receptors (GPCRs). Many predictions have been made about number C. neuropeptide GPCRs....

Abstract Neuronal communication involves small-molecule transmitters, gap junctions, and neuropeptides. While neurons often express multiple neuropeptides, our understanding of the coordination their actions mutual interactions remains limited. Here, we demonstrate that two NLP-10 FLP-1, released from same interneuron pair, AVKL/R, exert antagonistic effects on locomotion speed in Caenorhabditis elegans . accelerates by activating G protein-coupled receptor NPR-35 premotor interneurons...

Pathogenic infection elicits behaviors that promote recovery and survival of the host. After exposure to pathogenic bacterium Pseudomonas aeruginosa PA14, nematode Caenorhabditis elegans modifies its sensory preferences avoid pathogen. Here, we identify antagonistic neuromodulators shape this acquired avoidance behavior. Using an unbiased cell-directed neuropeptide screen, show AVK neurons upregulate release RF/RYamide FLP-1 neuropeptides during drive pathogen avoidance. Manipulations...

Gonadotropin-releasing hormone (GnRH) is a key regulator of reproductive maturation in humans and other vertebrates. Homologs GnRH its cognate receptor have been identified invertebrates-for example, the adipokinetic (AKH) corazonin (CRZ) neuropeptide pathways arthropods. However, precise evolutionary relationships origins these signalling systems remain unknown. Here we addressed this issue with first identification both GnRH-type CRZ-type deuterostome-the echinoderm (starfish) Asterias...

In response to environments that cause cellular stress, animals engage in sleep behavior facilitates recovery from the stress. Caenorhabditis elegans, stress-induced sleep(SIS) is regulated by cytokine activation of ALA neuron, which releases FLP-13 neuropeptides characterized an amidated arginine-phenylalanine (RFamide) C-terminus motif. By performing unbiased genetic screen for mutants impair somnogenic effects neuropeptides, we identified gene dmsr-1, encodes a G-protein coupled receptor...

In vertebrates thyrotropin-releasing hormone (TRH) is a highly conserved neuropeptide that exerts the hormonal control of thyroid-stimulating (TSH) levels as well neuromodulatory functions. However, functional equivalent in protostomian animals remains unknown, although TRH receptors are proto- and deuterostomians. Here we identify TRH-like precursor Caenorhabditis elegans belongs to bilaterian family precursors. Using CRISPR/Cas9 RNAi reverse genetics, show neuropeptides, through activation...

Sensitization is a simple form of behavioral plasticity by which an initial stimulus, often signaling danger, leads to increased responsiveness subsequent stimuli. Cross-modal sensitization important feature arousal in many organisms, yet its molecular and neural mechanisms are incompletely understood. Here we show that C. elegans, aversive mechanical stimuli lead both enhanced locomotor activity chemosensory pathways. Both cross-modal depend on the release FLP-20 neuropeptides from primary...

Abstract Maintaining or shifting between behavioral states according to context is essential for animals implement fitness-promoting strategies. How the integration of internal state, past experience and sensory inputs orchestrates persistent multidimensional changes remains poorly understood. Here, we show that C. elegans integrates environmental temperature food availability over different timescales engage in dwelling, scanning, global glocal search strategies matching thermoregulatory...

The circadian clock controls behavior and metabolism in various organisms. However, the exact timing strength of rhythmic phenotypes can vary significantly between individuals same species. This is highly relevant for rhythmically complex marine environments where organismal diversity likely permits occupation different microenvironments. When investigating locomotor Platynereis dumerilii , a model system molecular chronobiology, we found strain-specific, high variability individual worms....

Peptides and protein hormones form the largest group of secreted signals that mediate intercellular communication are central regulators physiology behavior in all animals. Phylogenetic analyses biochemical identifications peptide-receptor systems reveal a broad evolutionary conservation these signaling at molecular level. Substantial progress has been made recent years on characterizing physiological putative ancestral roles many peptide through comparative studies invertebrate models....

Abstract Vitellogenesis or maternal yolk formation is considered critical to the reproduction of egg-laying animals. In invertebrates, however, most its regulatory genes are still unknown. Via a combined mapping and whole-genome sequencing strategy, we performed forward genetic screen isolate novel regulators production in nematode model system Caenorhabditis elegans . addition isolating new alleles rab-35 , rab-10 M04F3.2 identified five mutant corresponding three potently suppressing...

Planarians display remarkable plasticity in maintenance of their germline, with the ability to develop or dismantle reproductive tissues response systemic and environmental cues. Here, we investigated role G protein-coupled receptors (GPCRs) this dynamic germline regulation. By genome-enabled receptor mining, identified 566 putative planarian GPCRs classified them into conserved phylum-specific subfamilies. We performed a functional screen identify NPYR-1 as cognate for NPY-8, neuropeptide...

The molecular mechanisms by which animals integrate external stimuli with internal energy balance to regulate major developmental and reproductive events still remain enigmatic. We investigated this aspect in the marine bristleworm, Platynereis dumerilii , a species where sexual maturation is tightly regulated both metabolic state lunar cycle. Our specific focus was on ligands receptors of gonadotropin-releasing hormone (GnRH) superfamily. Members superfamily are key triggering vertebrates...

Abstract Learning and memory are regulated by neuromodulatory pathways, but the contribution temporal requirement of most neuromodulators in a learning circuit unknown. Here we identify evolutionarily conserved neuromedin U (NMU) neuropeptide family as regulator C. elegans gustatory aversive learning. The NMU homolog CAPA-1 its receptor NMUR-1 required for retrieval learned salt avoidance. Gustatory requires release neuropeptides from sensory ASG neurons that respond to stimuli an...

Neuropeptides are ancient regulators of physiology and behaviour, but reconstruction neuropeptide evolution is often difficult owing to lack sequence conservation. Here, we report that the receptor for NGFFFamide in sea urchin Strongylocentrotus purpuratus (phylum Echinodermata) an orthologue vertebrate neuropeptide-S (NPS) receptors crustacean cardioactive peptide (CCAP) receptors. Importantly, this has facilitated two bilaterian signalling systems. Genes encoding precursor a...

Food availability and nutritional status are important cues affecting behavioral states. Here we report that, in Caenorhabditis elegans , a cascade of dopamine neuropeptide signaling acts to inhibit nociception food-poor environments. In the absence food, animals show decreased sensitivity increased adaptation soluble repellents sensed by polymodal ASH nociceptors. The effects food on affected signaling; via DOP-1 receptor decrease whereas receptors NPR-1 NPR-2 act increase off food....