All animals, including humans, use their sense of smell to learn about the nutritional, safety, and social states of their environments. Olfaction is orchestrated by olfactory sensory neurons expressing identical receptors, which target their axons to glomeruli in the olfactory bulb generating an olfactory map. Glomeruli are the elementary units of olfactory processing and organize information from the nose and transmit it to higher regions of the brain. Currently, the principles governing how this map is formed, organized, and interpreted to trigger thoughts, memories, emotions, and behaviors are not completely understood due to the complexity of the olfactory system. This proposal aims to understand the mechanisms governing axon targeting to glomeruli and to determine the anatomical relationships between olfactory receptors and their glomeruli. In my preliminary studies, I established a method to quantify olfactory receptor (OR) positions in the bulb. Using this approach, I have determined the anterior-posterior positions for 905 ORs.
Aim 1 seeks to comprehensively evaluate ORs in vitro to test the hypothesis that OR basal activity correlates with OSN axon- targeting along the anterior-posterior axis.
Aim 2 seeks to test the hypothesis that glomerular positions are stereotyped but not fixed and the positional variability can vary from OR to OR.
This proposal serves to advance our fundamental understanding of the olfactory system by elucidating the receptor identity and organization of glomeruli. Aim 1 will advance our understanding of GPCR structure and activity by investigating OR constitutive activity. Aim 2 will establish a map of OR projection targets, a resource that will assist fellow investigators in determining glomerular positional variability, sequence features defining glomerular position, and an understanding of the odor code.
