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

项目总结/摘要 嗅觉系统是一个理想的模型系统，可以用来研究感官刺激的高度加工过程。 具体和系统的方式。了解决定电路的基本概念， 嗅球（OB）是阐明OB神经元如何处理和代表气味的关键。基本气味 OB的编码单位是肾小球模块，由肾小球组成，肾小球是球形会聚 嗅觉感觉神经元（OSN）轴突表达相同的气味受体（OR），和突触后 这些OSN的目标。这些靶细胞包括二尖瓣和簇状（M/T）细胞，它们是来自神经元的主要投射神经元。 OB到皮质结构。OB表面的肾小球组织结构可靠、定型 在动物中，OSN OR表达在确定OSN靶向的位置中起主要作用， 肾小球形成然而，与单个核细胞相对应的M/T细胞的数量和空间分布与单个核细胞的数量和空间分布无关。 肾小球模块未知。在目标1中，我将确定肾小球体积（内在的）和肾小球体积（内在的）之间的关系。 或通过气味暴露而改变）以及对应于单个刺激的M/T细胞的数量和空间分布。 肾小球在目标2中，我将使用OR特异性气味条件反射来研究气味条件反射的时间和持续性。 单个肾小球的M/T细胞网络的气味诱发的结构变化。为了实现这些目标，我将 使用电穿孔来特异性标记与单个基因鉴定的肾小球相关的M/T细胞。我 初步研究结果表明，在M/T细胞的数量和空间分布方面，动物与动物之间具有相似性。 在M72肾小球模块中。我的数据还显示，肾小球体积发生了显著的、持续的变化， 出生前和出生后早期气味暴露后相关M/T细胞数量增加。我预测 P10前的气味暴露将导致M/T细胞网络的深刻和持久的结构变化， 激活的肾小球这些结果将不仅描述解剖的遗传鉴定 肾小球模块，而且还将增加我们对感觉系统的关键期的了解 解剖发展，从而解决嗅觉领域的基本知识差距。在 此外，这项工作与我对麻醉学的临床兴趣密切相关。理解基本的 感觉系统的回路对于研究麻醉剂干扰感觉系统的机制至关重要。 perception.因此，我建议结合严格的指导研究培训，纵向临床 经验，课程，以及专业和领导力发展活动。智力，技术， 在此奖学金培训期间完善的专业技能将有助于我 作为一个有抱负的医生科学家在学术麻醉学的临床领域的发展。

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.