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Background  Whole-genome association studies in humans have enabled the unbiased discovery of new genes associated with human memory performance. However, such studies do not allow for a functional or causal testing of newly identified candidate genes. Since polymorphisms in Calsyntenin 2 (CLSTN2) showed a significant association with episodic memory performance in humans, we tested the  C. elegans  CLSTN2 ortholog CASY-1 for possible functions in the associative behavior of  C. elegans .    Methodology/Principal Findings  Using three different associative learning paradigms and functional rescue experiments, we show that CASY-1 plays an important role during associative learning in  C. elegans . Furthermore, neuronal expression of human CLSTN2 in  C. elegans  rescues the learning defects of  casy-1  mutants. Finally, genetic interaction studies and neuron-specific expression experiments suggest that CASY-1 may regulate AMPA-like GLR-1 glutamate receptor signaling.    Conclusion/Significance  Our experiments demonstrate a remarkable conservation of the molecular function of  Calsyntenins  between nematodes and humans and point at a role of  C. elegans casy-1  in regulating a glutamate receptor signaling pathway.

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