Neuroligins are postsynaptic cell adhesion molecules, and mutations in two of the four human neuroligin genes are associated with a subset of cases of autism spectrum disorders (Jamain et al., 2003; Laumonnier et al., 2004; Yan et al., 2005). C. elegans has a single neuroligin gene (
nlg-1), and
nlg-1 null mutants display superficially normal growth, locomotion, and nervous system structure. Nevertheless, we have identified a number of specific behavioral phenotypes associated with
nlg-1 mutants. For example, when confronted with a thermal gradient,
nlg-1 mutants do not accumulate at their growth temperature, but instead move independently of temperature. This atactic behavior is independent of the temperature at which the animals were grown and their feeding state. In addition,
nlg-1 mutants have selective chemosensory deficits: they respond normally to many chemical attractants and repellants (both soluble and volatile) and to food, but they do not respond to the repellant n-octanol. Furthermore, although
nlg-1 mutants are similar to wild type in their attraction to diacetyl by itself and their avoidance of cupric acetate by itself, there is a dramatic difference in sensory processing when the two compounds are presented simultaneously in an "approach/avoidance" paradigm (Ishihara et al., 2002):
nlg-1 mutants are significantly more likely than wild type to cross a cupric acetate barrier placed between them and the attractant diacetyl. This response is different from responses of
hen-1 and
casy-1 mutants in the same paradigm:
hen-1 and
casy-1 mutants are significantly less likely than wild type to cross the cupric acetate barrier (Ishihara et al., 2002; Ikeda et al., 2008). In addition,
hen-1 and
casy-1 mutants also display deficits in behavioral plasticity mediated by paired stimuli (Ishihara et al., 2002; Ikeda et al., 2008), while
nlg-1 mutants have wild-type responses using such paradigms. Thus,
hen-1 and
casy-1 mutants have a quite different type of sensory processing deficit than
nlg-1 mutants. Finally, for each of these
nlg-1 mutant phenotypes, we have demonstrated rescue by transgenic expression of an NLG-1::YFP fusion protein. (Supported by a grant from Autism Speaks).