The overarching goal of this project is to address a fundamental question in neuroscience: how do sensory neural circuits support flexible behaviors? In nearly all animals, behavioral responses to sensory stimuli vary as a function of age, prior experience, nutritional state, and environment. However, the molecular and cellular mechanisms that enable animals to generate context-appropriate behaviors are poorly understood. This project will investigate the neural basis of behavioral flexibility using the response of the free-living nematode Caenorhabditis elegans to carbon dioxide (CO2) as a model system. It will elucidate the context-dependent changes in neural circuit function that determine whether CO2 is attractive, repulsive, or neutral to C. elegans. Because the survival of nearly all animals depends on the ability to adapt to changing internal and external conditions, this study will have broad implications for animal behavior. In addition, CO2 is a host cue for many harmful parasitic nematodes of humans, livestock, and plants. A better understanding of how nematodes respond to CO2 may enable the development of new strategies for preventing harmful nematode infections. In addition, CO2 response by C. elegans will be used as an educational platform for mentoring, teaching, and outreach activities designed to engage students of all levels in scientific research.
Preliminary studies conducted in the lab of the Principal Investigator demonstrated that CO2 response by C. elegans can be rapidly modulated by ambient oxygen (O2) levels and nutritional state such that CO2 can be either attractive, repulsive, or neutral. Modulation of the CO2 circuit may be attributable to changes in the extracellular signaling molecules used, changes in the interpretation of these signaling molecules by downstream neurons, or a combination of both. This proposal aims to distinguish among these possibilities using an integrated approach that includes molecular biology, genetics, calcium imaging, and behavioral analysis. By comparing the functional properties of the CO2 circuit under high vs. low O2 conditions and in well-fed vs. starved animals, and by elucidating the molecular pathways that regulate CO2 response under these different conditions, this work will pinpoint the specific molecular and cellular features of the CO2 circuit that determine the behavioral response to CO2. The results of this study will elucidate basic principles of circuit design that support flexible behavioral outputs. Many of the molecular pathways and circuit motifs that operate in nematodes also operate in other animals, including mammals. Thus, results from this study will be relevant to many other animal species.
