| We studied a neural circuit in C. elegans in which the ASH sensory neurons detect high osmolarity, touch to the nose, and the volatile repellant, octanol, and signal to the worm to move backward. Genetic and molecular evidence suggests that different signals are produced at the ASH-interneuron synapses in response to the different stimuli. The first part of this thesis describes a screen for mutants that have a defective avoidance response upon encountering regions of high osmolarity. The second portion of this thesis describes the cloning of the egl-3 gene, which encodes a prohormone convertase homolog that modulates ASH-interneuron signaling. An AMPA-type glutamate receptor (GluR) GLR-1 is expressed in synaptic targets of ASH, and these receptors are required for ASH-mediated touch sensitivity. We show here that mutations in the egl-3 gene restore ASH-mediated touch sensitivity to mutants lacking glr-1 GluRs. Laser ablation of the ASH neurons in glr-1; egl-3 double mutants eliminated the restored response indicating that egl-3 does not restore nose touch response by bypassing ASH signaling altogether. We also showed that egl-3 was unable to restore the nose touch response in animals defective in glutamate signaling. This suggests egl-3 mutants restore the nose touch response by modulating the effects of glutamate signaling in glr-1 mutants rather than by a completely independent mechanism. We showed that glr-1; egl-3 mutants not only have a restored nose touch response, they also fail to habituate to the response after the same number of trials that results in habituation in wild type or glr-1 mutant animals. These results suggest that neuropeptides can regulate the sensitivity of mechanosensory pathways in C. elegans, and they implicate neuropeptides in the mechanism for habituation of mechanosensory responses. |
