Olfactory sensory neurons in the nasal cavity send odor information to the olfactory bulb, the first central relay in this chemosensory system. Mitral and tufted cells in the bulb then transmit the information to the anterior olfactory nucleus (AON) and piriform cortex (PC). The AON plays a crucial role in the processing of olfactory stimuli: it provides feedforward information from the bulb to the PC, and is involved in the retrograde flow of information from the cortex to the bulb. Importantly, it also serves as the point of intercommunication between the left and right olfactory bulbs and cortices. As such, it plays a fundamental role in the processing olfactory information. Indeed, it will be impossible to understand the function of the olfactory forebrain without greater insight into the circuitry and function of the AON. The proposed studies focus on a single concept: understanding the organization of the AON. The proposed work will a) uncover the fine-scale morphology of the afferent inputs from the olfactory bulb, b) examine possible olfactory coding strategies in the AON, c) demonstrate the intrinsic organization and connections of the region, and d) elucidate differences in regional output patterns. Each of the studies examines interlocking but independent aspects of the problem. Furthermore, each study uses state-of-the-art techniques, correlating refined morphological analyses with broader functional studies. The goal is to begin to understand variations in regional organization and investigate the possibility of the existence of different neuronal phenotypes. The results will make the area accessible for further study from a molecular biological perspective. The information we gather will be important for many reasons, including our ability to understand and model olfactory function. By gathering fundamental data on the number of AON cells each bulb afferent contacts, what synaptic patterns exist within the AON, and whether output pathways diverge or converge, we will begin to understand the larger circuit that comprises the olfactory system. Relevance: a) A more complete understanding of the AON also has clinical relevance as there are indications that pathological changes in the region occur in Alzheimer's and Parkinson's diseases, suggesting that changes in the AON may significantly contribute to the well-documented deficits in olfactory function that occurs in aging, b) Sensory systems are crucial for humans to navigate through the world, interact and learn. The present research will shed substantial light on this process. ? ? ?
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