An opioid-like system regulating feeding behavior in C. elegans

Neuropeptides are essential for the regulation of appetite. Here we show that neuropeptides could regulate feeding in mutants that lack neurotransmission from the motor neurons that stimulate feeding muscles. We identified nlp-24 by an RNAi screen of 115 neuropeptide genes, testing whether they affected growth. NLP-24 peptides have a conserved YGGXX sequence, similar to mammalian opioid neuropeptides. In addition, morphine and naloxone respectively stimulated and inhibited feeding in starved worms, but not in worms lacking NPR-17, which encodes a protein with sequence similarity to opioid receptors. Opioid agonists activated heterologously expressed NPR-17, as did at least one NLP-24 peptide. Worms lacking the ASI neurons, which express npr-17, did not response to naloxone. Thus, we suggest that Caenorhabditis elegans has an endogenous opioid system that acts through NPR-17, and that opioids regulate feeding via ASI neurons. Together, these results suggest C. elegans may be the first genetically tractable invertebrate opioid model.

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The expression of delta opioid receptor mRNA in adult male zebra finches (Taenopygia guttata)

PLoS ONE ◽

10.1371/journal.pone.0256599 ◽

2021 ◽

Vol 16 (8) ◽

pp. e0256599

Author(s):

Pooja Parishar ◽

Neha Sehgal ◽

Soumya Iyengar

Keyword(s):

Opioid Receptors ◽

Sequence Similarity ◽

Expression Patterns ◽

Auditory Pathway ◽

Zebra Finches ◽

Endogenous Opioid System ◽

Endogenous Opioid ◽

High Sequence Similarity ◽

Brain Functions ◽

Song Control

The endogenous opioid system is evolutionarily conserved across reptiles, birds and mammals and is known to modulate varied brain functions such as learning, memory, cognition and reward. To date, most of the behavioral and anatomical studies in songbirds have mainly focused on μ-opioid receptors (ORs). Expression patterns of δ-ORs in zebra finches, a well-studied species of songbird have not yet been reported, possibly due to the high sequence similarity amongst different opioid receptors. In the present study, a specific riboprobe against the δ-OR mRNA was used to perform fluorescence in situ hybridization (FISH) on sections from the male zebra finch brain. We found that δ-OR mRNA was expressed in different parts of the pallium, basal ganglia, cerebellum and the hippocampus. Amongst the song control and auditory nuclei, HVC (abbreviation used as a formal name) and NIf (nucleus interfacialis nidopallii) strongly express δ-OR mRNA and stand out from the surrounding nidopallium. Whereas the expression of δ-OR mRNA is moderate in LMAN (lateral magnocellular nucleus of the anterior nidopallium), it is low in the MSt (medial striatum), Area X, DLM (dorsolateral nucleus of the medial thalamus), RA (robust nucleus of the arcopallium) of the song control circuit and Field L, Ov (nucleus ovoidalis) and MLd (nucleus mesencephalicus lateralis, pars dorsalis) of the auditory pathway. Our results suggest that δ-ORs may be involved in modulating singing, song learning as well as spatial learning in zebra finches.

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The Caenorhabditis elegans odr-2 Gene Encodes a Novel Ly-6-Related Protein Required for Olfaction

Genetics ◽

10.1093/genetics/157.1.211 ◽

2001 ◽

Vol 157 (1) ◽

pp. 211-224 ◽

Cited By ~ 1

Author(s):

Joseph H Chou ◽

Cornelia I Bargmann ◽

Piali Sengupta

Keyword(s):

Caenorhabditis Elegans ◽

Motor Neurons ◽

Amino Terminus ◽

Signaling Proteins ◽

Related Protein ◽

Olfactory Neurons ◽

Unique Role ◽

C Elegans ◽

Founding Member ◽

High Concentrations

Abstract Caenorhabditis elegans odr-2 mutants are defective in the ability to chemotax to odorants that are recognized by the two AWC olfactory neurons. Like many other olfactory mutants, they retain responses to high concentrations of AWC-sensed odors; we show here that these residual responses are caused by the ability of other olfactory neurons (the AWA neurons) to be recruited at high odor concentrations. odr-2 encodes a membrane-associated protein related to the Ly-6 superfamily of GPI-linked signaling proteins and is the founding member of a C. elegans gene family with at least seven other members. Alternative splicing of odr-2 yields three predicted proteins that differ only at the extreme amino terminus. The three isoforms have different promoters, and one isoform may have a unique role in olfaction. An epitope-tagged ODR-2 protein is expressed at high levels in sensory neurons, motor neurons, and interneurons and is enriched in axons. The AWC neurons are superficially normal in their development and structure in odr-2 mutants, but their function is impaired. Our results suggest that ODR-2 may regulate AWC signaling within the neuronal network required for chemotaxis.

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lag-1, a gene required for lin-12 and glp-1 signaling in Caenorhabditis elegans, is homologous to human CBF1 and Drosophila Su(H)

Development ◽

10.1242/dev.122.5.1373 ◽

1996 ◽

Vol 122 (5) ◽

pp. 1373-1383 ◽

Cited By ~ 12

Author(s):

S. Christensen ◽

V. Kodoyianni ◽

M. Bosenberg ◽

L. Friedman ◽

J. Kimble

Keyword(s):

Caenorhabditis Elegans ◽

Binding Sites ◽

Feedback Loop ◽

Target Genes ◽

Sequence Similarity ◽

Nematode Caenorhabditis Elegans ◽

C Elegans ◽

Downstream Target ◽

Binding Factor ◽

Flanking Regions

The homologous receptors LIN-12 and GLP-1 mediate diverse cell-signaling events during development of the nematode Caenorhabditis elegans. These two receptors appear to be functionally interchangeable and have sequence similarity to Drosophila Notch. Here we focus on a molecular analysis of the lag-1 gene (lin-12 -and glp-1), which plays a central role in LIN-12 and GLP-1-mediated signal transduction. We find that the predicted LAG-1 protein is homologous to two DNA-binding proteins: human C Promoter Binding Factor (CBF1) and Drosophila Suppressor of Hairless (Su(H)). Furthermore, we show that LAG-1 binds specifically to the DNA sequence RTGGGAA, previously identified as a CBF-1/Su(H)-binding site. Finally, we report that the 5′ flanking regions and first introns of the lin-12, glp-1 and lag-1 genes are enriched for potential LAG-1-binding sites. We propose that LAG-1 is a transcriptional regulator that serves as a primary link between the LIN-12 and GLP-1 receptors and downstream target genes in C. elegans. In addition, we propose that LAG-1 may be a key component of a positive feedback loop that amplifies activity of the LIN-12/GLP-1 pathway.

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Identification Of A Novel Gene Altered In The RQ1 Mutant Strain Affecting Motor Axon Migration In Caenorhabditis Elegans

10.32920/ryerson.14662620 ◽

2021 ◽

Author(s):

Haider Z. Naqvi

Keyword(s):

Caenorhabditis Elegans ◽

Axon Guidance ◽

Motor Neurons ◽

Genetic Background ◽

Germ Line ◽

Strong Indication ◽

Wild Type ◽

C Elegans ◽

Novel Gene ◽

Mutation Region

Novel genetic enhancer screens were conducted targeting mutants involved in the guidance of axons of the DA and DB classes of motor neurons in C. elegans. These mutations are expected in genes that function in parallel to the unc-g/Netrin pathway. The screen was conducted in an unc-5(e53) genetic background and enhancers of the axon guidance defects caused by the absence of UNC-5 were identified. Three mutants were previously identified in the screen called rq1, rq2 and rq3 and two additional mutants called H2-4 and M1-3, were isolated in this study. In order to identify the gene affected by the rq1 mutation, wild-type copies of genes in the mapped rq1 mutation region were injected into the mutants to rescue the phenotypic defects. This is a strong indication that the gene of interest is a novel gene called H04D03.1. Promising results indicate that the H04D03.1 protein also works in germ-line apoptosis.

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Endogenous opioid system in developing normal and jimpy oligodendrocytes: ? and ? opioid receptors mediate differential mitogenic and growth responses

Glia ◽

10.1002/(sici)1098-1136(199802)22:2<189::aid-glia10>3.0.co;2-u ◽

1998 ◽

Vol 22 (2) ◽

pp. 189-201 ◽

Cited By ~ 58

Author(s):

Pamela E. Knapp ◽

Katalin Maderspach ◽

Kurt F. Hauser

Keyword(s):

Opioid Receptors ◽

Opioid System ◽

Growth Responses ◽

Endogenous Opioid System ◽

Endogenous Opioid

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Uneven balance of power between hypothalamic peptidergic neurons in the control of feeding

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1802237115 ◽

2018 ◽

Vol 115 (40) ◽

pp. E9489-E9498 ◽

Cited By ~ 14

Author(s):

Qiang Wei ◽

David M. Krolewski ◽

Shannon Moore ◽

Vivek Kumar ◽

Fei Li ◽

...

Keyword(s):

Food Intake ◽

Feeding Behavior ◽

Dynamic Balance ◽

Endogenous Opioid System ◽

Endogenous Opioid ◽

Neuronal Projection ◽

Functional Understanding ◽

The Face ◽

The Moment ◽

Opposing Effects

Two classes of peptide-producing neurons in the arcuate nucleus (Arc) of the hypothalamus are known to exert opposing actions on feeding: the anorexigenic neurons that express proopiomelanocortin (POMC) and the orexigenic neurons that express agouti-related protein (AgRP) and neuropeptide Y (NPY). These neurons are thought to arise from a common embryonic progenitor, but our anatomical and functional understanding of the interplay of these two peptidergic systems that contribute to the control of feeding remains incomplete. The present study uses a combination of optogenetic stimulation with viral and transgenic approaches, coupled with neural activity mapping and brain transparency visualization to demonstrate the following: (i) selective activation of Arc POMC neurons inhibits food consumption rapidly in unsated animals; (ii) activation of Arc neurons arising from POMC-expressing progenitors, including POMC and a subset of AgRP neurons, triggers robust feeding behavior, even in the face of satiety signals from POMC neurons; (iii) the opposing effects on food intake are associated with distinct neuronal projection and activation patterns of adult hypothalamic POMC neurons versus Arc neurons derived from POMC-expressing lineages; and (iv) the increased food intake following the activation of orexigenic neurons derived from POMC-expressing progenitors engages an extensive neural network that involves the endogenous opioid system. Together, these findings shed further light on the dynamic balance between two peptidergic systems in the moment-to-moment regulation of feeding behavior.

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Distributed Rhythm Generators Underlie Caenorhabditis elegans Forward Locomotion

10.1101/141911 ◽

2017 ◽

Cited By ~ 1

Author(s):

Anthony D. Fouad ◽

Shelly Teng ◽

Julian R. Mark ◽

Alice Liu ◽

Pilar Alvarez-Illera ◽

...

Keyword(s):

Caenorhabditis Elegans ◽

Motor Neurons ◽

Animal Behavior ◽

Rhythm Generation ◽

Rhythmic Movements ◽

Neural Oscillators ◽

Motor Circuit ◽

C Elegans ◽

Body Regions ◽

Forward Locomotion

ABSTRACTCoordinated rhythmic movements are ubiquitous in animal behavior. In many organisms, chains of neural oscillators underlie the generation of these rhythms. In C. elegans, locomotor wave generation has been poorly understood; in particular, it is unclear where in the circuit rhythms are generated, and whether there exists more than one such generator. We used optogenetic and ablation experiments to probe the nature of rhythm generation in the locomotor circuit. We found that multiple sections of forward locomotor circuitry are capable of independently generating rhythms. By perturbing different components of the motor circuit, we localize the source of secondary rhythms to cholinergic motor neurons in the midbody. Using rhythmic optogenetic perturbation we demonstrate bidirectional entrainment of oscillations between different body regions. These results show that, as in many other vertebrates and invertebrates, the C. elegans motor circuit contains multiple oscillators that coordinate activity to generate behavior.

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The Atypical Rho GTPase CHW-1 Works With SAX-3/Robo to Mediate Axon Guidance in Caenorhabditis elegans

10.1101/265066 ◽

2018 ◽

Cited By ~ 1

Author(s):

Jamie K. Alan ◽

Sara Robinson ◽

Katie Magsig ◽

Rafael S. Demarco ◽

Erik A. Lundquist

Keyword(s):

Caenorhabditis Elegans ◽

Axon Guidance ◽

Motor Neurons ◽

Rho Gtpases ◽

Rho Gtpase ◽

Genetic Interaction ◽

Small Gtpases ◽

Axon Pathfinding ◽

Rho Proteins ◽

C Elegans

AbstractDuring development, neuronal cells extend an axon towards their target destination in response to a cue to form a properly functioning nervous system. Rho proteins, Ras-related small GTPases that regulate cytoskeletal organization and dynamics, cell adhesion, and motility, are known to regulate axon guidance. Despite extensive knowledge about canonical Rho proteins (RhoA/Rac1/Cdc42), little is known about the Caenorhabditis elegans (C. elegans) atypical Cdc42-like family members CHW-1 and CRP-1 in regards to axon pathfinding and neuronal migration. chw-1(Chp/Wrch) encodes a protein that resembles human Chp (Wrch-2/RhoV) and Wrch-1 (RhoU), and crp-1 encodes for a protein that resembles TC10 and TCL. Here, we show that chw-1 works redundantly with crp-1 and cdc-42 in axon guidance. Furthermore, proper levels of chw-1 expression and activity are required for proper axon guidance. When examining CHW-1 GTPase mutants, we found that the native CHW-1 protein is likely partially activated, and mutations at a conserved residue (position 12 using Ras numbering, position 18 in CHW-1) alter axon guidance and neural migration. Additionally, we showed that chw-1 genetically interacts with the guidance receptor sax-3 in PDE neurons. Finally, in VD/DD motor neurons, chw-1 works downstream of sax-3 to control axon guidance. In summary, this is the first study implicating the atypical Rho GTPases chw-1 and crp-1 in axon guidance. Furthermore, this is the first evidence of genetic interaction between chw-1 and the guidance receptor sax-3. These data suggest that chw-1 is likely acting downstream and/or in parallel to sax-3 in axon guidance.

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