Loss of CaMKI function disrupts salt aversive learning in C. elegans

AbstractThe ability to adapt behavior to environmental fluctuations is critical for survival of organisms ranging from invertebrates to mammals. Caenorhabditis elegans can learn to avoid sodium chloride when it is paired with starvation. This behavior is likely advantageous to avoid areas without food. While some genes have been implicated in this salt aversive learning behavior, critical genetic components, and the neural circuit in which they act, remain elusive. Here, we show that the sole worm ortholog of mammalian CaMKI/IV, CMK-1, is essential for salt aversive learning behavior in C. elegans. We find that CMK-1 acts in the primary salt-sensing ASE neurons to regulate this behavior. By characterizing the intracellular calcium dynamics in ASE neurons using microfluidics, we find that loss of cmk-1 leads to an altered pattern of sensory-evoked calcium responses that may underlie salt aversive learning. Our study implicates the conserved CaMKI/CMK-1 as an essential cell-autonomous regulator for behavioral plasticity to environmental salt in C. elegans.Significance StatementLike other animals, the nematode Caenorhabditis elegans depends on salt for survival and navigates toward high concentrations of this essential mineral. Because salt generates osmotic stress at high concentrations, it also threatens the survival of small terrestrial animals like C. elegans. A growing body of evidence indicates that C. elegans balances these factors through a process called salt aversive learning. We show that this behavior depends on expression of a calcium/calmodulin-dependent kinase, CMK-1, in the ASE salt sensing neurons and that salt-induced calcium signals in the ASE neurons are less sensitive to salt conditioning in animals lacking CMK-1 function. Our study identifies CMK-1 and sensory neurons as key factors in this form of behavioral plasticity.

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CaMK (CMK-1) and O-GlcNAc transferase (OGT-1) modulate mechanosensory responding and habituation in an interstimulus interval-dependent manner in Caenorhabditis elegans

10.1101/115972 ◽

2017 ◽

Cited By ~ 2

Author(s):

Evan L. Ardiel ◽

Troy A. McDiarmid ◽

Tiffany A. Timbers ◽

Kirsten C. Y. Lee ◽

Javad Safaei ◽

...

Keyword(s):

Caenorhabditis Elegans ◽

Interstimulus Interval ◽

Behavioral Plasticity ◽

Neural Circuit ◽

Model Organisms ◽

Dependent Manner ◽

Mechanical Stimuli ◽

C Elegans ◽

Mutant Phenotypes ◽

Glcnac Transferase

AbstractThe ability to learn is an evolutionarily conserved adaptation that remains incompletely understood. Genetically tractable model organisms facilitate mechanistic explanations of learning that span genetic, neural circuit, and behavioural levels. Many aspects of neural physiology, including processes that underlie learning (e.g. neurotransmitter release and long-lasting changes in synaptic strength), are regulated by brief and local changes in [μm] levels of free intracellular Ca2+. On this scale, changes in [Ca2+] activate many Ca2+-sensors, including the Ca2+/calmodulin-dependent kinases (CaMKs). Here we reveal that the Caenorhabditis elegans ortholog of CaMK1/4, CMK-1, functions in primary sensory neurons to regulate responses to mechanical stimuli and behavioral plasticity, specifically habituation, a conserved form of non-associative learning. The habituation phenotypes of cmk-1 mutants were dependent on interstimulus interval (ISI), such that CMK-1 slows habituation at short ISIs, but promotes it at long ISIs. We predicted potential CaMK phosphorylation targets from catalytic site analysis of the human and C. elegans CaMKs and mutant analysis of these candidates implicated O-linked N-acetylglucosamine (O-GlcNAc) transferase, OGT-1, in mechanosensitivity and learning. Cell specific rescue and knockdown experiments showed that both CMK-1 and OGT-1 function cell autonomously in mechanosensory neurons to modulate learning. Interestingly, despite their similar mutant phenotypes, detailed behavioral analysis of double mutants demonstrated that CMK-1 and OGT-1 act in parallel genetic pathways. Our research identifies CMK-1 and OGT-1 as co-expressed yet independent regulators of mechanosensitivity and learning.

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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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A Dynamic Body Model of the NematodeC. eleganswith Neural Oscillators

Journal of Robotics and Mechatronics ◽

10.20965/jrm.2005.p0318 ◽

2005 ◽

Vol 17 (3) ◽

pp. 318-326 ◽

Cited By ~ 10

Author(s):

Michiyo Suzuki ◽

◽

Takeshi Goto ◽

Toshio Tsuji ◽

Hisao Ohtake ◽

...

Keyword(s):

Computer Simulation ◽

Motor Control ◽

Caenorhabditis Elegans ◽

Neural Circuit ◽

Rhythmic Movement ◽

Circuit Model ◽

Neural Oscillators ◽

C Elegans ◽

Body Model ◽

Multicellular Organisms

The nematode Caenorhabditis elegans (C. elegans), a relatively simple organism in structure, is one of the most well-studied multicellular organisms. We developed a virtual C. elegans based on the actual organism to analyze motor control. We propose a dynamic body model, including muscles, controlled by a neural circuit model based on the actual nematode. The model uses neural oscillators to generate rhythmic movement. Computer simulation confirmed that the virtual C. elegans realizes motor control similar qualitatively to that of the actual organism. Specified classes of neurons are killed in the neural circuit model corresponding to actual unc mutants, demonstrating that resulting movement of the virtual C. elegans resembles that of actual mutants.

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Memory of recent oxygen experience switches pheromone valence in Caenorhabditis elegans

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1618934114 ◽

2017 ◽

Vol 114 (16) ◽

pp. 4195-4200 ◽

Cited By ~ 24

Author(s):

Lorenz A. Fenk ◽

Mario de Bono

Keyword(s):

Caenorhabditis Elegans ◽

Behavioral Plasticity ◽

Prior Experience ◽

Sensory Information ◽

Dependent Manner ◽

Oxygen Environment ◽

C Elegans ◽

Sustained Change ◽

Context Dependent ◽

Physiological Correlate

Animals adjust their behavioral priorities according to momentary needs and prior experience. We show that Caenorhabditis elegans changes how it processes sensory information according to the oxygen environment it experienced recently. C. elegans acclimated to 7% O2 are aroused by CO2 and repelled by pheromones that attract animals acclimated to 21% O2. This behavioral plasticity arises from prolonged activity differences in a circuit that continuously signals O2 levels. A sustained change in the activity of O2-sensing neurons reprograms the properties of their postsynaptic partners, the RMG hub interneurons. RMG is gap-junctionally coupled to the ASK and ADL pheromone sensors that respectively drive pheromone attraction and repulsion. Prior O2 experience has opposite effects on the pheromone responsiveness of these neurons. These circuit changes provide a physiological correlate of altered pheromone valence. Our results suggest C. elegans stores a memory of recent O2 experience in the RMG circuit and illustrate how a circuit is flexibly sculpted to guide behavioral decisions in a context-dependent manner.

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Caffeic and Dihydrocaffeic Acids Promote Longevity and Increase Stress Resistance in Caenorhabditis elegans by Modulating Expression of Stress-Related Genes

Molecules ◽

10.3390/molecules26061517 ◽

2021 ◽

Vol 26 (6) ◽

pp. 1517

Author(s):

Sofia M. Gutierrez-Zetina ◽

Susana González-Manzano ◽

Begoña Ayuda-Durán ◽

Celestino Santos-Buelga ◽

Ana M. González-Paramás

Keyword(s):

Oxidative Stress ◽

Caenorhabditis Elegans ◽

Phenolic Compounds ◽

Caffeic Acid ◽

Phenolic Acids ◽

Stress Resistance ◽

C Elegans ◽

High Concentrations ◽

Gene Expression Studies ◽

Stress Related Genes

Caffeic and dihydrocaffeic acid are relevant microbial catabolites, being described as products from the degradation of different phenolic compounds i.e., hydroxycinnamoyl derivatives, anthocyanins or flavonols. Furthermore, caffeic acid is found both in free and esterified forms in many fruits and in high concentrations in coffee. These phenolic acids may be responsible for a part of the bioactivity associated with the intake of phenolic compounds. With the aim of progressing in the knowledge of the health effects and mechanisms of action of dietary phenolics, the model nematode Caenorhabditis elegans has been used to evaluate the influence of caffeic and dihydrocaffeic acids on lifespan and the oxidative stress resistance. The involvement of different genes and transcription factors related to longevity and stress resistance in the response to these phenolic acids has also been explored. Caffeic acid (CA, 200 μM) and dihydrocaffeic acid (DHCA, 300 μM) induced an increase in the survival rate of C. elegans under thermal stress. Both compounds also increased the mean and maximum lifespan of the nematode, compared to untreated worms. In general, treatment with these acids led to a reduction in intracellular ROS concentrations, although not always significant. Results of gene expression studies conducted by RT-qPCR showed that the favorable effects of CA and DHCA on oxidative stress and longevity involve the activation of several genes related to insulin/IGF-1 pathway, such as daf-16, daf-18, hsf-1 and sod-3, as well as a sirtuin gene (sir-2.1).

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Calcium/Calmodulin-Dependent Protein Kinase II Regulates Caenorhabditis elegans Locomotion in Concert With a Go/Gq Signaling Network

Genetics ◽

10.1093/genetics/156.3.1069 ◽

2000 ◽

Vol 156 (3) ◽

pp. 1069-1082 ◽

Cited By ~ 5

Author(s):

Merrilee Robatzek ◽

James H Thomas

Keyword(s):

Caenorhabditis Elegans ◽

Protein Kinase ◽

Motor Neurons ◽

Direct Interaction ◽

Signaling Network ◽

Synaptic Activity ◽

Multiple Alleles ◽

C Elegans ◽

Calcium Calmodulin Dependent ◽

Protein Kinase Ii

Abstract Caenorhabditis elegans locomotion is a complex behavior generated by a defined set of motor neurons and interneurons. Genetic analysis shows that UNC-43, the C. elegans Ca2+/calmodulin protein kinase II (CaMKII), controls locomotion rate. Elevated UNC-43 activity, from a gain-of-function mutation, causes severely lethargic locomotion, presumably by inappropriate phosphorylation of targets. In a genetic screen for suppressors of this phenotype, we identified multiple alleles of four genes in a Go/Gq G-protein signaling network, which has been shown to regulate synaptic activity via diacylglycerol. Mutations in goa-1, dgk-1, eat-16, or eat-11 strongly or completely suppressed unc-43(gf) lethargy, but affected other mutants with reduced locomotion only weakly. We conclude that CaMKII and Go/Gq pathways act in concert to regulate synaptic activity, perhaps through a direct interaction between CaMKII and Go.

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Caenorhabditis elegans as an emerging model for studying the basic biology of anorectic effects of nicotine

10.1101/099952 ◽

2017 ◽

Author(s):

Robert Sobkowiak ◽

Piotr Kaczmarek ◽

Mateusz Kowalski ◽

Rafał Kabaciński ◽

Andrzej Lesicki

Keyword(s):

Body Size ◽

Caenorhabditis Elegans ◽

Food Intake ◽

Model Organism ◽

Growing Up ◽

C Elegans ◽

Nicotine Concentration ◽

Morphometric Methods ◽

Basic Biology ◽

High Concentrations

AbstractNicotine decreases food intake, and smokers often report that they smoke to control their weight. To see whether similar phenomena could be observed in the model organism Caenorhabditis elegans, we challenged drug-naϊve nematodes with a chronic low (0.01 mM) and high (1 mM) nicotine concentration for 55 h (from hatching to adulthood). After that, we recorded changes in their behavior in a nicotine gradient, where they could choose a desired nicotine concentration. By using a combination of behavioral and morphometric methods, we found that both nicotine and food modulate worm behavior. In the presence of food the nematodes adapted to the low nicotine concentration, when placed in the gradient, chose a similar nicotine concentration like C. elegans adapted to the high nicotine concentration. However, in the absence of food, the nematodes adapted to the low nicotine concentration, when placed in the gradient of this alkaloid, chose a similar nicotine concentration like naive worms. The nematodes growing up in the presence of high concentrations of nicotine had a statistically smaller body size, compared to the control condition, and the presence of food did not cause any enhanced slowing movement. These results provide a platform for more detailed molecular and cellular studies of nicotine addiction and food intake in this model organism.

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Attraction to pheromones in Caenorhabditis elegans can be reversed through associative learning

10.1101/476648 ◽

2018 ◽

Author(s):

M. Dal Bello ◽

A. Pérez-Escudero ◽

F. C. Schroeder ◽

J. Gore

Keyword(s):

Caenorhabditis Elegans ◽

Associative Learning ◽

Behavioral Plasticity ◽

Current Knowledge ◽

Natural Environments ◽

Chemical Signaling ◽

Learning Abilities ◽

C Elegans ◽

Pheromone Blend

AbstractDespite the ubiquity and importance of chemical signaling, we have only limited insight about the role of learning in the response to pheromones. Here, we demonstrate that responses to pheromones can be reprogrammed through associative learning. In particular, we show that attraction to ascaroside pheromones in the model nematode Caenorhabditis elegans can be reversed by training the animals to associate either a pheromone blend or single synthetic ascarosides with the lack of food. This behavioral plasticity alters worm preference for pheromones following consumption of a food patch, possibly improving foraging in natural environments. By bridging the gap between the current knowledge on the chemical language and the learning abilities of C. elegans, we provide insight on the possible links between learning and chemical signaling in animals.

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Requirements for branched chain amino acids and their interactions in the nematode Caenorhabditis elegans

Nematology ◽

10.1163/156854100509411 ◽

2000 ◽

Vol 2 (5) ◽

pp. 501-506 ◽

Cited By ~ 4

Author(s):

Dalia Perelman ◽

Nancy Lu

Keyword(s):

Amino Acids ◽

Amino Acid ◽

Caenorhabditis Elegans ◽

Branched Chain Amino Acids ◽

Nematode Caenorhabditis Elegans ◽

Optimal Range ◽

C Elegans ◽

Branched Chain Amino Acid ◽

High Concentrations ◽

Branched Chain

AbstractBranched chain amino acid (BCAA) requirements and their interactions were studied in the nematode Caenorhabditis elegans. Optimal, deficiency and toxic levels affecting nematode population growth were determined for each of the three BCAAs. The optimal range for leucine was 0.72-2.8; for isoleucine, 0.86-1.7; and for valine, 0.51-4.1 mg ml-1. Leucine at high concentrations was toxic. When isoleucine and valine were both added at high concentrations, they also exerted a marked toxic effect. The interactions of the branched chain amino acids found among vertebrate animals were not observed in C. elegans. Les besoins relatifs aux amino-acides en chaîne ramifiée et leurs interactions chez le nématode Caenorhabditis elegans - Les besoins relatifs aux amino-acides en chaîne ramifiée (BCAA) et leurs interactions ont été étudiés chez le nématode Caenorhabditis elegans. Les niveaux optimal, de déficience et toxique affectant la croissance de la population du nématode ont été déterminés pour chacune des BCAA. L'optimum est, pour la leucine de 0,72 à 2,8, pour l'isoleucine de 0,86 à 1,7 et pour la valine de 0,51 à 4,1 mg ml-1. A forte concentration la leucine est toxique. Si l'isoleucine et la valine sont ajoutées à forte concentration elles exercent également une action toxique prononcée. Les interactions entre BCAA observées chez les vertébrés ne l'ont pas été chez les C. elegans.

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Behavior of Caenorhabditis elegans in a nicotine gradient modulated by food

10.1101/079699 ◽

2016 ◽

Author(s):

Robert Sobkowiak ◽

Piotr Kaczmarek ◽

Mateusz Kowalski ◽

Rafał Kabaciński ◽

Andrzej Lesicki

Keyword(s):

Body Size ◽

Caenorhabditis Elegans ◽

Food Intake ◽

Model Organism ◽

Growing Up ◽

C Elegans ◽

Nicotine Concentration ◽

Morphometric Methods ◽

Drug Naïve ◽

High Concentrations

AbstractNicotine decreases food intake, and smokers often report that they smoke to control their weight. To see whether similar phenomena could be observed in the model organism Caenorhabditis elegans, we challenged drug-naïve nematodes with a chronic low (0.01 mM) and high (1 mM) nicotine concentration for 55 h (from hatching to adulthood). After that, we recorded changes in their behavior in a nicotine gradient, where they could choose a desired nicotine concentration. By using a combination of behavioral and morphometric methods, we found that both nicotine and food modulate worm behavior. In the presence of food the nematodes adapted to the low nicotine concentration, when placed in the gradient, chose a similar nicotine concentration like C. elegans adapted to the high nicotine concentration. However, in the absence of food, the nematodes adapted to the low nicotine concentration, when placed in the gradient of this alkaloid, chose a similar nicotine concentration like naïve worms. The nematodes growing up in the presence of high concentrations of nicotine had a statistically smaller body size, compared to the control condition, and the presence of food did not cause any enhanced slowing movement. These results provide a platform for more detailed molecular and cellular studies of nicotine addiction and food intake in this model organism.

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