A Conserved Function of C. elegans CASY-1 Calsyntenin in Associative Learning

Hoerndli, Frédéric; Walser, Michael; Hoier, Erika Fröhli; Quervain, Dominique J.‐F. de; Papassotiropoulos, Andreas; Hajnal, Alex

doi:10.1371/journal.pone.0004880

Cited by 39 publications

(42 citation statements)

References 29 publications

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“…It has been reported that calsyntenins are involved in learning and memory in both Caenorhabditis elegans and humans (143,249). Interestingly, calsyntenin function has been highly conserved during evolution, and human calsyntenin-2 can rescue associative learning phenotypes in C. elegans calsyntenin-1 mutants (132). The ectodomain of calsyntenin is required for learning (143).…”

Section: E Calsyntenin/alcadeinmentioning

confidence: 99%

Cadherins in Brain Morphogenesis and Wiring

Hirano

Takeichi

2012

Physiological Reviews

260

312

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LHirano S, Takeichi M. Cadherins in Brain Morphogenesis and Wiring. Physiol Rev 92: 597-634, 2012; doi:10.1152/physrev.00014.2011 -dependent cell-cell adhesion molecules that play critical roles in animal morphogenesis. Various cadherin-related molecules have also been identified, which show diverse functions, not only for the regulation of cell adhesion but also for that of cell proliferation and planar cell polarity. During the past decade, understanding of the roles of these molecules in the nervous system has significantly progressed. They are important not only for the development of the nervous system but also for its functions and, in turn, for neural disorders. In this review, we discuss the roles of cadherins and related molecules in neural development and function in the vertebrate brain.

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Section: E Calsyntenin/alcadeinmentioning

confidence: 99%

Cadherins in Brain Morphogenesis and Wiring

Hirano

Takeichi

2012

Physiological Reviews

260

312

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“…CASY-1 functions parallel to the insulin pathway in salt conditioning, as casy-1;ins-1 doublemutants had a more severe learning defect than either single mutant (Ikeda et al 2008). casy-1 mutants were also impaired in olfactory and thermosensory starvation conditioning assays (Ikeda et al 2008;Hoerndli et al 2009). In olfactory conditioning, casy-1 appears to be acting in a glr-1 pathway (Hoerndli et al 2009), as the glr-1;casy-1 double-mutant was as impaired as either single mutant.…”

Section: Casy-1mentioning

confidence: 99%

“…casy-1 mutants were also impaired in olfactory and thermosensory starvation conditioning assays (Ikeda et al 2008;Hoerndli et al 2009). In olfactory conditioning, casy-1 appears to be acting in a glr-1 pathway (Hoerndli et al 2009), as the glr-1;casy-1 double-mutant was as impaired as either single mutant. Furthermore, glr-1 overexpression rescued the learning defect of casy-1 mutants.…”

Section: Casy-1mentioning

confidence: 99%

An elegant mind: Learning and memory in Caenorhabditis elegans

Ardiel¹,

Rankin²

2010

Learn. Mem.

234

191

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This article reviews the literature on learning and memory in the soil-dwelling nematode Caenorhabditis elegans. Paradigms include nonassociative learning, associative learning, and imprinting, as worms have been shown to habituate to mechanical and chemical stimuli, as well as learn the smells, tastes, temperatures, and oxygen levels that predict aversive chemicals or the presence or absence of food. In each case, the neural circuit underlying the behavior has been at least partially described, and forward and reverse genetics are being used to elucidate the underlying cellular and molecular mechanisms. Several genes have been identified with no known role other than mediating behavior plasticity.Historically, it was believed that even if they were capable of learning, the nervous systems of invertebrates were too different to be instructive on human cognition. In the 1960s, Kandel and colleagues began studying learning in the marine mollusc Aplysia (Kandel and Tauc 1965). Using this system, they were able to relate behavioral plasticity to changes at specific synapses of identified neurons, and began a biochemical analysis of these neuronal changes, uncovering a role for cAMP, PKA, and CREB. In the 1970s, Benzer and colleagues began a genetic dissection of learning in the fruit fly Drosophila melanogaster (Quinn et al. 1974;Dudai et al. 1976). They established an associative learning assay (Quinn et al. 1974) and conducted a forward genetic screen, identifying the first learning mutant, dunce (Dudai et al. 1976). Since then, many genes have been cloned, and the biological basis of learning has proven to be highly conserved (Barco et al. 2006;Skoulakis and Grammenoudi 2006). Today there is no question as to the relevance of invertebrate research in the field of learning and memory.At about the same time that Kandel was beginning his work with Aplysia, Sydney Brenner chose Caenorhabditis elegans as the organism in which to study development and the nervous system (Brenner 1974). Today this transparent nematode is the world's best understood animal. It's small size ( 1 mm), short life cycle (,3 d), and ease of cultivation make it perfect for the laboratory, and its mode of reproduction is ideal for genetic analysis-selffertilizing hermaphrodites can be easily inbred or crossed with males. The genome has been mapped and sequenced, and there are thousands of mutants and RNAi constructs readily available for researchers. Furthermore, C. elegans has an invariant cell lineage and relatively simple morphology-959 cells make up the entire adult hermaphrodite (Sulston and Horvitz 1977;Sulston et al. 1983). Using serial section electron micrographs, White et al. (1986) were able to construct a neural wiring diagram of the hermaphrodite's 302 neurons. They found about 5000 chemical synapses, 600 gap junctions, and 2000 neuromuscular junctions, the location of which were fairly consistent between animals. With its invariant cell lineage and reproducible connectome, C. elegans was initially viewed as a genetically hardwired ...

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“…Calsyntenins seem to play a role in postsynaptic signaling (Hintsch et al, 2002). Casy-1 found in C. elegans is a homologue of human CLSTN2 (Hoerndli, Walser, & Frohli, 2009). Importantly, casy-1 mutants show deficits in associative learning paradigms and expression of human CLSTN2 reverses the behavioral deficits of casy-1 mutants (Hoerndli et al, 2009;Ikeda et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

KIBRA and CLSTN2 polymorphisms exert interactive effects on human episodic memory

Preuschhof

Heekeren

et al. 2010

Neuropsychologia

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a b s t r a c tIndividual differences in episodic memory are highly heritable. Several studies have linked a polymorphism in the gene encoding the KIBRA protein to episodic memory performance. Results regarding CLSTN2, the gene encoding the synaptic protein calsyntenin 2, have been less consistent, possibly pointing to interactions with other genes. Given that both KIBRA and CLSTN2 are expressed in the medial temporal lobe and have been linked to synaptic plasticity, we investigated whether KIBRA and CLSTN2 interactively modulate episodic memory performance (n = 383). We replicated the beneficial effect of the KIBRA T-allele on episodic memory, and discovered that this effect increases with the associative demands of the memory task. Importantly, the memory-enhancing effect of the KIBRA T-allele was boosted by the presence of the CLSTN2 C-allele, which positively affected memory performance in some previous studies. In contrast, the presence of CLSTN2 C-allele led to reduced performance in subjects homozygous for the KIBRA C-allele. Overall, these findings suggest that KIBRA and CLSTN2 interactively modulate episodic memory performance, and underscore the need for delineating the interactive effects of multiple genes on brain and behavior.

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A Conserved Function of C. elegans CASY-1 Calsyntenin in Associative Learning

Cited by 39 publications

References 29 publications

Cadherins in Brain Morphogenesis and Wiring

Cadherins in Brain Morphogenesis and Wiring

An elegant mind: Learning and memory in Caenorhabditis elegans

KIBRA and CLSTN2 polymorphisms exert interactive effects on human episodic memory

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