Signal transduction through heterotrimeric G proteins is critical for sensory response across species. Regulator of G protein signaling (RGS) proteins are negative regulators of signal transduction. C. elegans RGS-3 (C29H12.3) is expressed exclusively in nine pairs of sensory neurons (ASH, ADL, AWB, AWC, ASI, ASJ, ASK, PHA and PHB), suggesting that it may act to regulate signal transduction and the behavioral responses mediated by these neurons. To test this hypothesis, we identified
rgs-3(
vs19), a recessive loss-of-function deletion allele. Since RGS proteins generally act to dampen signaling, we expected
rgs-3 mutant animals to have enhanced signaling in sensory neurons and, therefore, to be hypersensitive to environmental stimuli. Instead, we find that
rgs-3 animals are defective in their ability to respond to many chemical stimuli. For two odorants, however,
rgs-3 animals respond as well as N2 animals when the concentration of the odorant is reduced. We find that loss of RGS-3 leads to aberrantly increased G protein-coupled calcium signaling in sensory neurons, but decreased synaptic output, ultimately leading to behavioral defects. Thus,
rgs-3 responses are restored by decreasing G protein-coupled signal transduction genetically, by expressing a calcium binding protein to buffer calcium levels in sensory neurons, or by enhancing glutamatergic synaptic transmission from sensory neurons to interneurons. We also find that feeding status alters the sensitivity of
rgs-3 mutant animals to strong stimuli; the presence of food restores behavioral responses. Serotonin and dopamine are two neurotransmitters released upon exposure to food. However, exogenous serotonin, which increases calcium signaling in sensory neurons, exacerbates the
rgs-3 behavioral defects. Conversely, exogenous dopamine mimics food and restores
rgs-3 behavioral responses to strong sensory stimuli, suggesting that dopamine may normally function to dampen sensory signaling. Consistent with this observation, we find that
cat-2 mutant animals, which lack a tyrosine hydroxylase enzyme required for dopamine biosynthesis, are hypersensitive to a dilute chemical stimulus.