An animal’s decision on how to respond to the environment is based not only on the sensory information available, but further depends on internal factors such as stress, sleep / wakefulness, hunger / satiety and experience. Neurotransmitters and neuropeptides in the brain modulate neural circuits accordingly so that appropriate behaviors are generated. Aberrant neuromodulation is implicated in diseases such as insomnia, obesity or anorexia. Given the complexity of most neural systems studied, we lack good models of how neuromodulators systemically affect the activities of neural networks.To overcome this problem, I propose to study neural circuits in the nematode C. elegans, which is a genetically tractable model organism with a simple and anatomically defined nervous system. I will focus on the neural circuits involved in oxygen chemosensory behaviors. Worms can smell oxygen and they use this information to navigate through heterogeneous environments. This enables them to find food and to engage in social interactions. Oxygen chemosensory behaviors are highly modulated by experience and nutritional status, but the underlying mechanisms are not understood.I established behavioral assays that allow studying the modulation of oxygen behaviors in a rigorously quantifiable manner. I also acquired expertise in micro-fabrication technologies and developed imaging devices to measure the activity of neurons in live animals. The first two aims of this proposal focus on the application of these technologies to study (A) how neuropeptides mediate experience dependent modulation of oxygen chemosensory circuits; and (B) how food availability and nutritional status modulate the same neural circuits. Aim (C) is an innovative engineering approach in which I will develop new microfluidic technologies that allow the simultaneous recording of oxygen evoked behaviors and neural activity. This will be beneficial for aims A and B and will pave way for new future research directions.