PROJECT SUMMARY / ABSTRACT Our long-term goal is to define general principles that connect neuronal activity to unconstrained behaviors in natural sensory environments. Achieving this goal will require the development of new tools to quantitatively compare behavior across species in complex environments and to monitor neural activity in freely moving an- imals. Here we propose to bring together a diverse, multi-disciplinary team of five labs with a track record of productively measuring and modeling neural activity and behavior. We will use two parallel approaches to make progress towards imaging neural activity from freely moving small genetic model organisms as they navigate complex sensory environments. In Aim 1 we will develop behavioral apparatus that allows for experimenter control of sensory stimuli (mechanosensory flow, odor, and visual stimuli) while monitoring unconstrained be- havior at two resolutions. Low resolution measurements allow for quantification of stimulus-guided navigation, while high resolution measurements allow for detailed quantification of body posture and limb kinematics, and will eventually permit imaging of neural activity. In Aim 2, we will develop bioluminescence-based transgenic animals and techniques for imaging neural activity in freely moving flies and fish. Optimization of these reagents and protocols will allow for eventual simultaneous measurements of neural activity and behavior in larger and more complex environments. This work draws on our collective expertise in quantitative behavior, biolumines- cent indicators, real-time tracking of animal behavior at high resolution, and physical modeling of animal behav- ior. This work will advance technologies for studying neural activity in unconstrained animals and establish a collaborative team to pursue this work.