Neuronal activity has been implicated in the establishment and maintenance of appropriate synaptic connections in vertebrate and invertebrate systems. However, the molecular mechanisms by which neuronal activity affects connectivity are poorly understood. To understand this process, we have focused our studies on the PHB phasmid sensory neurons. The PHB neurons mediate an aversive response to low concentrations of sodium dodecyl sulfate (SDS) (Hilliard et al., Current Biology, 2002). In response to SDS, PHB neurons terminate backward movement via their connections with AVA interneurons. Our preliminary results using the WincG.2 cGMP biomarker (a kind gift from N. L’Etoile) indicate that exposure to behaviorally relevant concentrations of SDS results in an increase in cGMP in PHB sensory neurons. We are currently taking a genetic approach to elucidating the pathway by which SDS is sensed by the phasmid neurons using a high throughput assay adapted from the method developed by Hilliard and colleagues (Current Biology, 2002). Using this assay, we find that odr-3/Gαolf and tax-2/CNG-channel β subunit, in addition to previously discovered tax-4/CNG-channel α subunit (Hilliard et al., Current Biology, 2002), are required for SDS chemosensation. To determine if defects in sensory signaling affect sensory synapses, we utilized the split-GFP-based trans-synaptic marker NLG-1 GRASP (Neuroligin-1 GFP Reconstitution Across Synaptic Partners) to visualize synapses between PHBs and AVA interneurons in live animals. Interestingly, we find that odr-3/Gαolf mutants have synapses that are normal at the L1 stage but significantly reduced in later larval stages, while phasmid neuron morphology appears normal. Cell-specific rescue experiments indicate that odr-3/Gαolf functions in PHB neurons. Subcellular localization of odr-3/Gαolf shows localization to the PHB cilia, consistent with a role in sensory signaling being required to maintain synaptic integrity. These results indicate that C. elegans may be a powerful model organism for elucidating the molecular mechanisms by which sensory activity affects synaptic connectivity. Our future goals are to identify the remainder of the chemosensory signaling pathway and to further characterize the mechanism by which sensory activity maintains synapses using molecular genetic and physiological approaches. Funded by NIH (1R01NS087544 to MV at SJSU and NL at UCSF, 5T34GM008253 MARC undergraduate fellowship to CV, 2R25GM071381 RISE undergraduate fellowships to CV and JP), HHMI (SCRIBE 52006312 undergraduate fellowship to BB and KM), and NSF (RUMBA REU 1004350 fellowship to KA and EH).