A major role of the nervous system is to sense and integrate external and internal cues in the context of past experience and current conditions, and translate this information into behavioral outputs. The intracellular and intercellular signaling pathways by which neuronal networks generate defined, yet adaptive behaviors are not well understood. The study of thermosensory behaviors in C. elegans provides an excellent system in which to explore the pathways by which a small, hard-wired neuronal network generates highly complex and experience-dependent behaviors. The behavior of C. elegans on a thermal gradient is governed by a 'memory' of its cultivation temperature (Tc), such that animals exhibit defined behaviors in specific temperature ranges relative to Tc. Tc memory is plastic and can be reset upon cultivation of animals at a new temperature. The overall goal of this proposal is to describe the mechanisms by which sensory transduction, plasticity and communication among thermosensory neurons generate robust, yet flexible behaviors in an experience- and context-dependent manner. The Specific Aims are to: 1) Examine the role of CaMKI/IV-mediated regulation of gene expression in setting Tc memory in the AFD thermosensory neurons. Tc memory is in part encoded by the response threshold of the AFD thermosensory neurons. This aim will test the hypothesis that activity-regulated changes in the expression of AFD-expressed signaling genes sets their response threshold, and that these changes are mediated by a CaMKI/IV cascade. 2) Explore the role of neuromodulation in setting the operating range of the ASI thermosensory neurons. Although AFD was the only previously known thermosensory neuron type, we have now shown that the ASI sensory neurons are also thermosensory, and exhibit a Tc-dependent operating range. The operating range of ASI may be set by AFD via peptidergic neuromodulation. This aim will utilize highly quantitative behavioral assays, in vivo imaging, and optogenetic manipulations to describe the mechanisms by which AFD signals to ASI to coordinate their response ranges. 3) Investigate mechanisms of thermotransduction and plasticity in the AWC thermosensory neurons. In addition to AFD and ASI, we showed that the AWC olfactory neurons are also thermosensory. The goal of this aim is to define molecular mechanisms of thermotransduction in AWC, and to explore the hypothesis that AWC represents the locus of starvation-induced behavioral plasticity in the circuit. Work from our lab has uncovered unexpected complexity in thermosensory processing at the periphery. The proposed experiments will elucidate the mechanisms by which coordination and communication among multiple thermosensory neuron types ensures a coherent behavioral output. Given the remarkable conservation of signaling pathways, synaptic mechanisms and circuit functions across species, this work will provide new information about sensory processing and plasticity in more complex nervous systems.