Rose JK et al. (2002) Learn Mem "A new group-training procedure for habituation demonstrates that presynaptic glutamate release contributes to long-term memory in Caenorhabditis elegans."

Rankin CH, Kaun KR, Rose JK

[Learn Mem, 2002]

In the experiments reported here we have developed a new group-training protocol for assessing long-term memory for habituation in Caenorhabditis elegans. We have replicated all of the major findings of the original single-worm protocol using the new protocol: (1) distributed training produced long-term retention of training, massed training did not; (2) distributed training at long interstimulus intervals (ISIs) produced long-term retention, short ISIs did not; and (3) long-term memory for distributed training is protein synthesis-dependent as it could be blocked by heat shock during the inter-block interval. In addition, we have shown that long-term memory for habituation is graded, depending on the number of blocks of stimuli in training. The inter-block interval must be >40 min for long-term retention of training to occur. Finally, we have tested long-term memory for habituation training in a strain of worms with a mutation in a vesicular glutamate transporter in the sensory neurons that transduce tap (eat-4). The results from these eat-4 worms indicate that glutamate release from the sensory neurons has an important role in the formation of long-term memory ror habituation.

Beck CDO et al. (1997) Anim Learn Behav "Long-term habituation is produced by distributed training at long ISIs and not by massed training or short ISIs in Caenorhabditis elegans."

Beck CDO, Rankin CH

[Anim Learn Behav, 1997]

To begin an investigation of the cellular processes that underlie long-term memory in the nematode Caenorhabditis elegans, it is first necessary to determine that C. elegans is capable of retention over 24 h, and to investigate the factors that may influence the expression of long-term memory. In the present study, the effects of stimuli number, interstimulus interval (ISI), and training procedure on longterm retention of habituation were tested in C. elegans. At a long (60-sec) ISI, distributed training sessions produced long-term habituation retained for 24 h, whereas massed training sessions or training with few stimuli did not. When training was performed at a short (10-sec) ISI, long-term habituation was not detectable with testing at either a 10- or a 60-sec ISI. The long-term habituation observed after distributed training sessions at a 60-sec ISI was consistently expressed when the training procedures were varied. Thus it is clear that C. elegans can reliably express long-term retention for distributed training sessions at a 60-sec ISI, making the system a candidate for further investigations into the cellular processes supporting memory.

Briga M et al. (2015) Exp Gerontol "What can long-lived mutants tell us about mechanisms causing ageing and lifespan variation in natural environments?"

Briga M, Verhulst S

[Exp Gerontol, 2015]

Long-lived mutants of model organisms have brought remarkable progress in our understanding of ageing mechanisms. However, long-lived mutants are usually maintained in optimal standardized laboratory environments (SLEs), and it is not obvious to what extent insights from long-lived mutants in SLEs can be generalized to more natural environments. To address this question we reviewed experiments that compared the fitness and lifespan advantage of long-lived mutants relative to their wild type controls in SLEs and more challenging environments. In competition experiments over multiple generations, the long-lived mutants had a lower fitness relative to wild type controls, and this disadvantage was clearest when the environment included natural challenges such as limited food (N=6 studies ranging from yeast to mice). It is well known that most long-lived mutants have impaired reproduction, which provides one reason for the fitness disadvantage. However, based on 12 experiments in various model organisms such as the nematode worm C. elegans, the fruitfly D. melanogaster and the mouse Mus musculus, we found that the lifespan advantage of long-lived mutants is diminished in more challenging environments, often to the extent that the wild type controls outlive the long-lived mutants. Thus, it appears that information on ageing mechanisms obtained from long-lived mutants in SLEs may be specific to such environments, because those same mechanisms do not extend lifespan in more natural environments. This suggests that different mechanisms cause variation in ageing and lifespan in SLEs compared to natural populations.

Lee Lau H et al. (2013) Genes Brain Behav "Genetic dissection of memory for associative and non-associative learning in Caenorhabditis elegans."

Timbers TA, Lee Lau H, Rankin CH, Mahmoud R

[Genes Brain Behav, 2013]

The distinction between non-associative and associative forms of learning has historically been based on the behavioral training paradigm. Through discovering the molecular mechanisms that mediate learning, we can develop a deeper understanding of the relationships between different forms of learning. Here, we genetically dissect short- and long-term memory for a non-associative form of learning, habituation and an associative form of learning, context conditioning for habituation, in the nematode Caenorhabditis elegans. In short-term chemosensory context conditioning for habituation, worms trained and tested in the presence of either a taste (sodium acetate) or smell (diacetyl) context cue show greater retention of habituation to tap stimuli when compared with animals trained and tested without a salient cue. Long-term memory for olfactory context conditioning was observed 24 h after a training procedure that does not normally induce 24 h memory. Like long-term habituation, this long-term memory was dependent on the transcription factor cyclic AMP-response element-binding protein. Worms with mutations in glr-1 [a non-N-methyl-d-aspartate (NMDA)-type glutamate receptor subunit] showed short-term but not long-term habituation or short- or long-term context conditioning. Worms with mutations in nmr-1 (an NMDA-receptor subunit) showed normal short- and long-term memory for habituation but did not show either short- or long-term context conditioning. Rescue of nmr-1 in the RIM interneurons rescued short- and long-term olfactory context conditioning leading to the hypothesis that these interneurons function to integrate information from chemosensory and mechanosensory systems for associative learning.

Zagoriy V et al. (2010) Chem Biodivers "Long-chain O-ascarosyl-alkanediols are constitutive components of Caenorhabditis elegans but do not induce dauer larva formation."

Kurzchalia T, Matyash V, Zagoriy V

[Chem Biodivers, 2010]

Two long-chain ascarosides, O-ascarosylnonacosane-2,28-diol and O-ascarosyluntriacontane-2,30-diol, were isolated from Caenorhabditis elegans and detected in all developmental stages of the worm. The long-chain ascarosides were shown to be minor lipid components, and it was also shown that they do not induce dauer larva formation.

Rose JK et al. (2022) Front Behav Neurosci "Neuroligin Plays a Role in Ethanol-Induced Disruption of Memory and Corresponding Modulation of Glutamate Receptor Expression."

Liang J, Lin CHS, Rose JK, Parvand M, Butterfield M, Rankin CH

[Front Behav Neurosci, 2022]

Exposure to alcohol causes deficits in long-term memory formation across species. Using a long-term habituation memory assay in Caenorhabditis elegans, the effects of ethanol on long-term memory (> 24 h) for habituation were investigated. An impairment in long-term memory was observed when animals were trained in the presence of ethanol. Cues of internal state or training context during testing did not restore memory. Ethanol exposure during training also interfered with the downregulation of AMPA/KA-type glutamate receptor subunit (GLR-1) punctal expression previously associated with long-term memory for habituation in C. elegans. Interestingly, ethanol exposure alone had the opposite effect, increasing GLR-1::GFP punctal expression. Worms with a mutation in the C. elegans ortholog of vertebrate neuroligins (nlg-1) were resistant to the effects of ethanol on memory, as they displayed both GLR-1::GFP downregulation and long-term memory for habituation after training in the presence of ethanol. These findings provide insights into the molecular mechanisms through which alcohol consumption impacts memory.

Rose JK et al. (2003) J Neurosci "GLR-1, a non-NMDA glutamate receptor homolog, is critical for long-term memory in Caenorhabditis elegans."

Kaun KR, Rankin CH, Chen SH, Rose JK

[J Neurosci, 2003]

Long-term memory for habituation to tap in Caenorhabditis elegans depends on glr-1, a homolog of mammalian non-NMDA glutamate receptors; mutations in glr-1 blocked long-term memory formation. Green fluorescent protein (GFP) constructs were used to visualize glr-1 expression in the interneurons of the mechanosensory circuit and synaptobrevin in the tap sensory neurons of trained and untrained worms. Trained animals had less GLR-1::GFP expression than untrained animals; there was no difference in the vesicle marker synaptobrevin. Heat shock during training blocked both the behavioral expression of long-term memory and the change in GLR-1::GFP expression. Thus, long-term memory in C. elegans is dependent on glr-1 and likely involves changes in the expression or

Blackwell TK et al. (2002) Genes Dev "Getting the right dose of repression."

Walker AK, Blackwell TK

[Genes Dev, 2002]

In recent years, it has become apparent that eukaryotic transcriptional repression mechanisms are remarkably varied in their modes of action and effects. Repression can be established by proteins that act over a short range, or at a long distance. Some mechanisms of repression are readily reversible, but others establish a heritable state of long-term silencing...

Watanabe Y et al. (1997) Biochim Biophys Acta "cDNA sequence of a translational elongation factor Ts homologue from Caenorhabditis elegans: mitochondrial factor-specific features found in the nematode homologue peptide."

Watanabe K, Kita K, Ueda T, Watanabe Y

[Biochim Biophys Acta, 1997]

The cDNA for a homologue of elongation factor Ts which probably functions in mitochondria has been sequenced from a nematode Caenorhabditis elegans. The deduced amino acid sequence (316 amino acids long) has a possible transit peptide sequence at the amino terminus and several common specific features for mammalian mitochondrial EF-Ts. The amino acid identities in the protein from C. elegans compared with those of bovine mitochondria and Escherichia coli are 29.5% and 24.0%, respectively. The C. elegans sequence was classified as a long EF-Ts (ca. 280 amino acids long) similar to peptides from mammalian mitochondria and eubacteria other than Thermus and cyanobacteria (except Spirulina platensis), rather than short EF-Ts (ca. 200 amino acids long) as those of Thermus, cyanobacteria and plastids.

Flavell, Steven W et al. (2013) International Worm Meeting "Serotonin and PDF are opposing neuromodulators that control a bistable foraging behavior in C. elegans."

Pokala, Navin, Albrecht, Dirk A, Macosko, Evan Z, Bargmann, Cornelia I, Larsch, Johannes, Flavell, Steven W

[International Worm Meeting, 2013]

Foraging animals have distinct exploration and exploitation behaviors that are organized into discrete, long-lasting behavioral states. Here we characterize a neuromodulatory circuit that generates such long-lasting roaming and dwelling states in Caenorhabditis elegans. We find that two opposing neuromodulators, serotonin and the neuropeptide pigment dispersing factor (PDF), each initiate and extend one behavioral state. Serotonin promotes dwelling states through the MOD-1 serotonin-gated chloride channel. The spontaneous activity of serotonergic neurons correlates with dwelling behavior, and optogenetic modulation of the critical MOD-1-expressing targets induces long-lasting dwelling states. PDF promotes roaming states through the Gas-coupled PDFR-1 receptor; optogenetic activation of cAMP production in PDFR-1-expressing cells induces long-lasting roaming states. The neurons that produce and respond to each neuromodulator form a distributed circuit orthogonal to the classical wiring diagram, with several essential neurons that express each molecule. The slow temporal dynamics of the neuromodulatory circuit supplement fast motor circuits to give rise to long-lasting behavioral states.