Despite the critical role mechanical stimuli play in hearing and touch, the molecular basis of mechanosensation in vertebrates remains elusive. The proposed research uses genetic, cellular, and molecular techniques in C. elegans to identify receptor proteins, signal transduction pathways and synaptic pathways involved in the detection of noxious mechanical and chemical stimuli. The C. elegans ASH neurons respond to nose touch, high osmolarity, and volatile repellents. Mutations have been identified which perturb responses to specific ASH stimuli. The genes involved will be molecularly characterized. They will address the role of the OSM-10 protein in osmosensation, and examine newly identified peptidergic neurotransmitters in the ASH circuit.