We tested 4 strains carrying distinct transposon insertions in or near the aay locus. All 4 strains exhibited increased ethanol-induced hyperactivity, and 3 exhibited reduced ethanol sedation sensitivity and sedation tolerance (Table 1 and Table S5). One transposon insertion, S042314, was previously shown to affect the aay locus, and when homozygous resulted in axon guidance defects in the embryonic peripheral nervous system (Prokopenko et al., 2000). Additionally, flies homozygous for a transposon insertion in the CG3011 locus, encoding the enzyme that converts glycine to serine, also exhibited increased ethanol-induced hyperactivity (Table S5). Expression of aay and CG3011 were strongly up-regulated by ethanol exposure in all studies carried out to date in flies (Morozova et al., 2006; Urizar et al., 2007). These data suggest that genes in the serine synthesis pathway negatively regulate ethanol-induced hyperactivity and may also promote ethanol sedation sensitivity.
