Neuroligin and neurexin are cell adhesion molecules that are sufficient to induce synaptogenesis in cultured mammalian cells (Fu et al., 2003; Nam et al., 2005). Mutations in neuroligin are associated with a subset of cases of the developmental disorder autism (Jamain et al., 2003). We have tested transcriptional fusion constructs using the
nlg-1 regulatory sequences to drive the expression of a YFP reporter. We found that YFP expression is limited to neurons in the head, ventral nerve cord and tail. In double reporter studies, GABAergic neurons do not express
nlg-1. Instead,
nlg-1 is expressed in a portion of cholinergic cells, particularly in the ventral nerve cord. In addition, many of the
nlg-1 positive cells in the head are neither cholinergic nor GABAergic. Surprisingly, neuroligin knockout animals do not exhibit obvious cholinergic defects. Instead, they exhibit phenotypes that are similar to those of an AMPA type glutamate receptor (
glr-1) knockout. The neuroligin expressing cholinergic neurons also express
glr-1 glutamate receptors, and receive input from putative glutamate-releasing interneurons. Neuroligin knockout worms have a lower frequency of spontaneous reversal, although when these worms do reverse, the reversal is of the same duration as wildtype worms. This phenotype is similar to that of
glr-1 mutants. Another behavioral phenotype of neuroligin knockout mutants is a defect in thermotaxis. Well fed wildtype worms placed on a thermal gradient preferentially track to the temperature at which they were raised. The
nlg-1 and
glr-1 knockout animals do not accumulate at a specific temperature; instead, these worms move independently of ambient temperature. Our working hypothesis is that neuroligin is required for proper localization of
glr-1. We are testing this hypothesis by introducing a
glr-1::GFP functional fusion into a neuroligin knockout background to assess the effect of
nlg-1 on
glr-1::GFP localization.