Project Summary The long-term goal of our research is to understand how the sensory environment regulates animal behavior. In this proposal, we will focus on investigating the genetic and neural basis of two sensory modalities: thermosensation and osmosensation. The ability to sense temperature and osmolarity is essential for life. Defects in thermosensation and osmosensation cause various neurological, renal and metabolic disorders. A key player in thermosensation and osmosensation is the molecular sensory receptors that detect thermal and osmotic cues. However, the molecular identities of cold-sensing receptors that sense cold temperatures are poorly understood. Similarly, no osmolarity-sensing receptors have thus far been definitively identified in any metazoan organisms. C. elegans is a popular genetic model organism widely used for the study of sensory biology. To survive the harsh environment, C. elegans has evolved a rich repertoire of sensory systems. Like mammals, C. elegans possesses the sense of temperature and osmolarity. Here, we propose to investigate the genetic and neural mechanisms by which animals sense temperature, particularly cold temperature, as well as osmolarity using C. elegans as a model. To do so, we will take a multifaceted approach that integrates molecular genetics, behavioral analysis, laser ablation, whole-brain imaging, and electrophysiology. As the mechanisms underlying thermosensation and osmosensation, particularly those involving sensory receptors, tend to be evolutionarily conserved, the proposed work will provide novel insights into our understanding of thermosensation and osmosensation in humans and their related neurological, renal and metabolic disorders.