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Mutations in the presenilin (PS) genes are a predominant cause of familial Alzheimer's disease (fAD). An ortholog of PS in the genetic model organism Caenorhabditis elegans (C. elegans) is sel-12. Mutations in the presenilin genes are commonly thought to lead to fAD by upregulating the expression of amyloid beta (Aβ), however this hypothesis has been challenged by recent evidence. As C. elegans lack amyloid beta (Aβ), the goal of this work was to examine Aβ-independent effects of mutations in sel-12 and PS1/PS2 on behaviour and sensory neuron morphology across the lifespan in a C. elegans model. Olfactory chemotaxis experiments were conducted on sel-12(ok2078) loss-of-function mutant worms. Adult sel-12 mutant worms showed significantly lower levels of chemotaxis to odorants compared to wild-type worms throughout their lifespan, and this deficit increased with age. The chemotaxis phenotype in sel-12 mutant worms is rescued by transgenic over-expression of human wild-type PS1, but not the classic fAD-associated variant PS1C410Y, when expression was driven by either the endogenous sel-12 promoter (Psel-12), a pan-neuronal promoter (Primb-1), or by a promoter whose primary expression was in the sensory neurons responsible for the chemotaxis behavior (Psra-6, Podr-10). The behavioural phenotype was also rescued by over-expressing an atypical fAD-linked mutation in PS1 (PS1ΔS169) that has been reported to leave the Notch pathway intact. An examination of the morphology of polymodal nociceptive (ASH) neurons responsible for the chemotaxis behavior also showed increased neurodegeneration over time in sel-12 mutant worms that could be rescued by the same transgenes that rescued the behaviour, demonstrating a parallel with the observed behavioral deficits. Thus, we report an Aβ-independent neurodegeneration in C. elegans that was rescued by cell specific over-expression of wild-type human presenilin. [ABSTRACT FROM AUTHOR]

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.