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 to how the brain to updates its stimulus-encoding scheme from a synthetic to 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 will be conducted at Harvard University in the laboratories of Prof. Venkatesh Murthy and Prof. Naoshige Uchida. Together with my mentors and advisory committee, I have developed a comprehensive training plan that will provide me with new technical skills and provide professional development that will enable my successful transition to an independent investigator. The completion of this project will provide the basis for future experiments related to learning-mediated plasticity in the olfactory system and other sensory systems.
Olfactory dysfunction is often a first symptom of several neurodegenerative diseases, including Alzheimer's disease and Parkinson's disease. A better understanding of the basic neural circuitry and functional properties of the olfactory system may provide clues to the etiology of these diseases, as well as potential diagnostic mechanisms.