PROJECT SUMMARY/ABSTRACT To reliably encode information about the environment, neurons must modify their activity profiles and even connectivity to accurately interpret complex stimuli. Cortical feedback projections to the olfactory bulb are uniquely positioned at the interface between detection-based processing that is driven by sensory input and analytical processing occurring in the piriform cortex. This arrangement makes these projections an ideal target to study how learning reshapes neuronal activity profiles. I have developed an approach that will allow for a comprehensive analysis of the axonal activity of principal neurons in the piriform cortex, while mice learn a task requiring them to identify a specific odor embedded in complex mixtures, thereby providing unique insight into olfactory scene analysis. My approach will also provide a detailed analysis of the connectivity between cortical axons and their postsynaptic targets in the olfactory bulb, which will reveal how the olfactory bulb integrates processed information from the piriform cortex. The hypothesis I will test is that learning reshapes cortico-fugal input to the olfactory bulb, leading to enhanced odor-scene segmentation through the disambiguation of olfactory bulb output neuron activity profiles. The outcomes of these studies will provide novel insight into how the brain updates its stimulus-encoding scheme from a synthetic to an analytical representation of a stimulus environment. The studies proposed here are novel technically as well as conceptually, and the results will be broadly applicable to other sensory systems. In Aim 1, I will characterize how learning shapes the activity of cortical feedback projections to the olfactory bulb. Aim 2 will determine how the synaptic strength and number of cortical inputs to individual olfactory modules are updated during learning. Finally, Aim 3 will determine how cortical input shapes the activity profiles of bulbar output neurons. The training phase of this award was conducted at Harvard University in the laboratories of Prof. Venkatesh Murthy and Prof. Naoshige Uchida. This award will support a Diversity Fellow in my independent laboratory at the University of Illinois at Chicago to provide her technical skills in the laboratory, academic preparation, and professional development necessary to successfully apply to top graduate programs.