PROJECT SUMMARY A fundamental step in understanding sensation is understanding how neural circuits in the brain transform patterns of sensory neuron activity into robust and efficient representations of the external world. Sensation is an active process in which the detection and initial encoding of sensory information is dynamically modulated by sampling behavior. Understanding how central circuits process sensory information in the context of active sampling is critical for understanding the neural basis of sensation in the behaving animal. The goals of this project are to understand how neural circuits in the mammalian olfactory bulb transform sensory inputs in vivo and in the context of active odor sampling, or sniffing. First, we will examine circuit-level determinants of the diverse patterns of excitatory drive onto mitral and tufted cells, focusing on the respective roles of sensory inputs and glomerular circuits in generating this diversity. Second, we will define if and how stimulus features themselves – in particular, odorant chemistry and intensity – relate to the dynamics of excitatory drive onto MT cells, as well as how these dynamics are shaped by sniffing behavior. Finally, we will ask how dynamics and glomerular patterns of excitatory input impact the input-output transformation of the olfactory bulb. The proposed experiments implement several innovative approaches to dissecting circuit function in the intact olfactory bulb; these include using second-generation optical reporters of glutamate to directly image excitatory signaling onto mitral/tufted cells with high temporal resolution, dual-color imaging of glutamate and calcium to simultaneously monitor presynaptic inputs and readouts of mitral/tufted cell activity from the same glomerulus, and the use of identified glomeruli with well-characterized response spectra to design powerful tests of model predictions. The overall impact of the project will be to advance a mechanistic understanding of the relationship between the dynamics of odor sampling and the resulting dynamics of neural activity in the olfactory bulb. These findings will pave the way for ultimately understanding the role that neural dynamics and active sampling play in odor perception.