Organization and plasticity of post-synaptic targets of individual glomeruli in the mammalian olfactory bulb

项目总结/文摘

Project Summary/Abstract The olfactory system is an ideal model system in which to study the processing of sensory stimuli in a highly specific and systematic manner. Understanding the fundamental concepts that dictate the circuitry of the olfactory bulb (OB) is crucial to elucidating how OB neurons process and represent odorants. The basic odor coding unit of the OB is the glomerular module, comprised of a glomerulus, which is a spherical convergence of olfactory sensory neuron (OSN) axons expressing the same odorant receptor (OR), and the post-synaptic targets of these OSNs. These targets include mitral and tufted (M/T) cells, the main projection neurons from the OB to cortical structures. The organization of glomeruli on the surface of the OB is reliable and stereotyped across animals, with OSN OR expression playing a major role in determining the location of OSN targeting and glomerulus formation. However, the number and spatial distribution of M/T cells corresponding to a single glomerular module is unknown. In Aim 1, I will determine the relationship between glomerulus volume (intrinsic or changed by odorant exposure) and the number and spatial distribution of M/T cells corresponding to a single glomerulus. In Aim 2, I will use OR-specific odorant conditioning to investigate the timing and persistence of odorant-evoked structural changes to the M/T cell network of a single glomerulus. To achieve these aims, I will use electroporation to specifically label the M/T cells associated with single genetically-identified glomeruli. My preliminary findings demonstrate animal-to-animal similarity in the number and spatial distribution of M/T cells within the M72 glomerular module. My data also show significant, persistent glomerular volume changes and increases in associated M/T cell number following prenatal and early postnatal odorant exposure. I predict that odorant exposure prior to P10 will cause profound and persistent structural changes to the M/T cell network of an activated glomerulus. These results will not only describe the anatomy of genetically identified glomerular modules, but will also increase our understanding of the critical period of sensory system anatomical development, thus addressing a fundamental knowledge gap in the field of olfaction. In addition, this work integrates closely with my clinical interest in anesthesiology. Understanding the fundamental circuitry of sensory systems is critical to the study of mechanisms by which anesthetics perturb sensory perception. Thus, I propose a combination of rigorous mentored research training, longitudinal clinical experiences, coursework, and professional and leadership development activities. The intellectual, technical, and professional skills refined during this fellowship training period will be instrumental in my development as an aspiring physician scientist in the clinical field of academic anesthesiology.