Dopamine signaling plays significant roles in modulating behavior and in learning. Its molecular mechanisms in vivo, however, are complex and still unclear. We have found that dopamine signaling is required for a novel type of behavioral plasticity in C. elegans (Kimura, Fujita and Katsura, in revision). The avoidance behavior of animals to a repulsive odor 2-nonanone is significantly enhanced rather than reduced after 1 h preexposure to the odor, and this enhancement involves dopamine signaling. Unlike previously identified dopamine-regulated behavioral plasticities in C. elegans, which require the presence of food for dopamine action (Sawin et al., 2000; Hills et al., 2004; Sanyal et al., 2004; Kindt et al., 2007), the enhancement of 2-nonanone avoidance is food-independent, suggesting a new role of dopamine signaling in the regulation of behavioral responses. Genetic and pharmacological studies have revealed that one of the D2-like dopamine receptor homologs
dop-3 is involved in the enhancement of 2-nonanone avoidance behavior. To identify the cellular site of action of
dop-3, we are conducting neuron-specific rescue experiments with
dop-3 mutants that exhibits the enhancement-defective phenotype. Various promoters for subsets of neurons were fused to
dop-3 cDNA for the rescue experiments and to fluorescent protein to study the expression patterns. Expression of
dop-3 cDNA in the neurons that are reportedly required to regulate locomotion (ventral nerve cord motor neurons with
acr-2 or
unc-47 promoters; Chase et al., 2004) or CREB expression (RIC interneurons with
tdc-1 promoter or SIA with
ceh-17; Suo et al., 2009) did not rescue the enhancement-defective phenotype while pan-neuronal expression (with the H20 promoter; a gift from Dr. Takeshi Ishihara) rescued the phenotype, suggesting that
dop-3 functions at a new site of action to enhance the avoidance behavior. We continue the rescue experiment to identify neuron(s) for the
dop-3 action. We thank Drs. Satoshi Suo (Mt. Sinai Hospital, Canada) for the
dop-3 cDNA and Yuichi Iino and Masahiro Tomioka (U. Tokyo, Japan) for the promoter library.