Vasopressin/Oxytocin-Related Signaling Regulates Gustatory Associative Learning in
            <i>C. elegans</i>

Beets, Isabel; Janssen, Tom; Meelkop, Ellen; Temmerman, Liesbet; Suetens, Nick; Rademakers, Suzanne; Jansen, Gert; Schoofs, Liliane

doi:10.1126/science.1226860

Cited by 168 publications

(196 citation statements)

References 62 publications

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“…These pNPs regulate several aspects of physiology, including sexual behavior and reproduction (GnRH, achatin, oxytocin, and GnIH/SIFamide), diuresis (CRF/diuretic hormone, calcitonin, and vasopressin), gut and heart activity (achatin, luqin, and orcokinin), pain perception (opioid), and food intake (NPY, kinins, neuromedin-U, galanin/allatostatin-A, and orexin/allatotropin). These pNPs may have originated concomitantly with the origin of a complex bilaterian body plan having a through gut with novel controls for food intake and digestion, excretory and circulatory systems, light-controlled reproduction (50), a centralized nervous system (76), complex reproductive behavior (77,78), and learning (79). The stable association of receptor-ligand families across bilateria revealed the long-term coevolution of receptor-ligand pairs.…”

Section: Resultsmentioning

confidence: 99%

Global view of the evolution and diversity of metazoan neuropeptide signaling

Jékely

2013

Proc. Natl. Acad. Sci. U.S.A.

418

651

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Neuropeptides are signaling molecules that commonly act via G protein-coupled receptors (GPCRs) and are generated in neurons by proneuropeptide (pNP) cleavage. Present in both cnidarians and bilaterians, neuropeptides represent an ancient and widespread mode of neuronal communication. Due to the inherent difficulties of analyzing highly diverse and repetitive pNPs, the relationships among different families are often elusive. Using similarity-based clustering and sensitive similarity searches, I obtained a global view of metazoan pNP diversity and evolution. Clustering revealed a large and diffuse network of sequences connected by significant sequence similarity encompassing one-quarter of all families. pNPs belonging to this cluster were also identified in the early-branching neuronless animal Trichoplax adhaerens. Clustering of neuropeptide GPCRs identified several orthology groups and allowed the reconstruction of the phyletic distribution of receptor families. GPCR phyletic distribution closely paralleled that of pNPs, indicating extensive conservation and long-term coevolution of receptor-ligand pairs. Receptor orthology and intermediate sequences also revealed the homology of pNPs so far considered unrelated, including allatotropin and orexin. These findings, together with the identification of deuterostome achatin and luqin and protostome opioid pNPs, extended the neuropeptide complement of the urbilaterian. Several pNPs were also identified from the hemichordate Saccoglossus kowalevskii and the cephalochordate Branchiostoma floridae, elucidating pNP evolution in deuterostomes. Receptor-ligand conservation also allowed ligand predictions for many uncharacterized GPCRs from nonmodel species. The reconstruction of the neuropeptide-signaling repertoire at deep nodes of the animal phylogeny allowed the formulation of a testable scenario of the evolution of animal neuroendocrine systems.Platynereis | proenkephalin | Petromyzon N europeptides are diverse neuron-secreted peptides with neuromodulatory, neurotransmitter, or hormonal functions. Most neuropeptides signal via G protein-coupled receptors (GPCRs) (1), with a few exceptions (2-8). As modulators of neuronal activity, neuropeptides contribute to the generation of different outputs from the same neuronal circuit in a context-dependent manner (9), or orchestrate complex motor programs (10). Many neuropeptides act as hormones and are released into the haemolymph by neurohemal organs, such as the vertebrate pituitary gland, or the insect corpora cardiaca (11). These peptide hormones regulate various aspects of physiology, including growth, metabolism, and reproduction. Active neuropeptides are generated from an inactive proneuropeptide (pNP) that contains a single or multiple copies of active peptides. Active peptides are commonly short, with only a few families adopting well-defined, but unrelated, folds (e.g., prolactin and glycoprotein hormones). pNPs have a signal peptide (SP) and enter the secretory apparatus where dedicated proteases cleave them at mono...

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Section: Resultsmentioning

confidence: 99%

Global view of the evolution and diversity of metazoan neuropeptide signaling

Jékely

2013

Proc. Natl. Acad. Sci. U.S.A.

418

651

View full text Add to dashboard Cite

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“…Other examples of functional analogy between orthologous protostome and deuterostome PSs include the cholecystokinin/sulfakinin that are involved in satiety (22) in humans and worms, and GnRH and AKH that have analogous functions in reproduction in both humans and worms (20). Two recent studies (43,44) showed that a bona fide vasopressin system was present in C. elegans and that it might participate in ancient circuits that control adaptive reproductive behaviors.…”

Section: Discussionmentioning

confidence: 99%

“…It will be particularly interesting in the future to study the function of these genes in the amphioxus and lophotrochozoan species to learn more about the conserved features of these vertebrate PSs. Recently, several PSs have been characterized in the nematode, including vasopressin (43,44). We give predictions for C. elegans peptides that had not been characterized to date, which include TK, DH31/Calc, SIFa, LK, luqin, and AstA, B, and C (Dataset S1).…”

Section: Discussionmentioning

confidence: 99%

Molecular evolution of peptidergic signaling systems in bilaterians

Mirabeau

Joly

2013

Proc. Natl. Acad. Sci. U.S.A.

385

707

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Peptide hormones and their receptors are widespread in metazoans, but the knowledge we have of their evolutionary relationships remains unclear. Recently, accumulating genome sequences from many different species have offered the opportunity to reassess the relationships between protostomian and deuterostomian peptidergic systems (PSs). Here we used sequences of all human rhodopsin and secretin-type G protein-coupled receptors as bait to retrieve potential homologs in the genomes of 15 bilaterian species, including nonchordate deuterostomian and lophotrochozoan species. Our phylogenetic analysis of these receptors revealed 29 wellsupported subtrees containing mixed sets of protostomian and deuterostomian sequences. This indicated that many vertebrate and arthropod PSs that were previously thought to be phyla specific are in fact of bilaterian origin. By screening sequence databases for potential peptides, we then reconstructed entire bilaterian peptide families and showed that protostomian and deuterostomian peptides that are ligands of orthologous receptors displayed some similarity at the level of their primary sequence, suggesting an ancient coevolution between peptide and receptor genes. In addition to shedding light on the function of human G protein-coupled receptor PSs, this work presents orthology markers to study ancestral neuron types that were probably present in the last common bilaterian ancestor. neuropeptide evolution | GPCR evolution | bilaterian CNS cell types | bilaterian brain evolution

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“…Mutants worms lacking nematocin (an AVP/OT-related neuropeptide) or its receptor were subjected to an associative learning paradigm using a short-term gustatory plasticity assay (56). The results suggested that defects in the nematocin signaling cascade disrupted gustatory associative learning and the facilitated experience-driven modulation of sodium chloride chemotaxis.…”

Section: Oxytocin In Learning and Memorymentioning

confidence: 99%

Learning About Oxytocin: Pharmacologic and Behavioral Issues

Chini

Leonzino

Braida

et al. 2014

Biological Psychiatry

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Despite the accumulating evidence suggesting that the neuropeptide oxytocin (OT) plays a role in neuropsychiatric disorders characterized by social dysfunction, the influence of OT on the nonsocial aspects of learning and memory have been less investigated. To foster research in this area, we review the effects of OT on learning and memory in animal models and humans. In healthy animal models, OT improves memory consolidation and extinction, but only if given at a low dose immediately after the acquisition phase. On the contrary, OT effects in healthy humans have been inconsistent; although, in this case, OT was always given before the acquisition phase and no dose-response curves have ever been drawn up. Interestingly, a specific impairment in the reversal of learning has been found in mice devoid of OT receptors and OT has been demonstrated to enhance fear extinction in rodents. All together, these data suggest that OT plays a role in elementary forms of behavioral flexibility and adaptive responses and support its therapeutic potential in neuropsychiatric disorders characterized by cognitive inflexibility and/or impairment (autism, schizophrenia, Alzheimer's disease, Parkinson disease, stroke, posttraumatic stress disorder). Accordingly, OT has been shown to improve cognitive flexibility in OT receptordeficient mice, and scattered findings indicate that intranasal OT has positive effects on the memory of patients with schizophrenia or posttraumatic stress disorders. Further studies of the therapeutic potential of OT as an enhancer of learning and memory are warranted.

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Vasopressin/Oxytocin-Related Signaling Regulates Gustatory Associative Learning in C. elegans

Cited by 168 publications

References 62 publications

Global view of the evolution and diversity of metazoan neuropeptide signaling

Global view of the evolution and diversity of metazoan neuropeptide signaling

Molecular evolution of peptidergic signaling systems in bilaterians

Learning About Oxytocin: Pharmacologic and Behavioral Issues

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