It is unclear how a single sensory neuron can distinguish between a variety of external stimuli and how the sensory circuit can generate distinct behavioral responses. The C. elegans ASH sensory neurons are required to detect volatile repellent chemicals (1-octanol and benzaldehyde), high osmolarity, and touch to the nose. We hope to reveal the sensory and synaptic mechanisms involved by studying the ASH sensory circuit. To address these questions, we focus our attention on modality specific genes which are required for response to one or two stimuli but not required for response to other stimuli detected by the ASH neurons. We conducted a behavioral screen to identify genes required for octanol avoidance. octanol avoidance defective-1
(rt68) (
oca-1 ) animals are severely defective in their response to hyperosmolarity, octanol or benzaldehyde, but their response to nose touch is normal.
oca-1(
rt68) animals habituate to nose touch and they can respond to odorants and soluble compounds detected by AWA, AWC, and ASE sensory neurons.
oca-1 encodes a small, previously uncharacterized protein with putative homologs in invertebrates and vertebrates. We are in the process of elucidating the function of OCA-1 using cellular, biochemical and genetic approaches. Interestingly, response to octanol is modulated by serotonin. Another modality specific mutation,
rt6 , shows transient defects in octanol avoidance.
rt6 mutant animals respond as well as normal animals to octanol on the bacterial lawn. After 10 minutes off the bacterial lawn,
rt6 mutant animals are severely defective in their response to octanol, but they can respond to octanol after 60 minutes off food. The
rt6 mutant phenotype can be rescued by the presence of food and 5mM serotonin. In C. elegans and other organisms, serotonin acts as neurotransmitter or neurohormone to regulate behavior. The
rt6 transient defect is surprising as the feeding status of C. elegans normally does not affect response to octanol. We have found that C. elegans sensitivity to octanol is increased in the presence of food. Consistent with our results,
tph-1(
m280) and
dgk-1(
nu62) mutant animals, which are defective in serotonin mediated signal pathway(Sze JY et al., Nature. 403:560-4, 2000. Nurrish S et al., Neuron 24:231-42, 1999), show decreased octanol sensitivity even in the presence of food. These mutant animals mimic the behavior of normal animals off food. The application of exogenous serotonin fails to rescue the defective octanol response of eat- 4 ,
osm-9 or
odr-3 mutant strains. As the corresponding genes encode a vesicular glutamate transporter, a TRP ion channel, and a G-alpha protein which are all necessary for ASH-meditated sensory signal transduction, we conclude that serotonin modulates synaptic signaling in the ASH circuit.