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

项目摘要/摘要 嗅觉系统是研究感觉刺激高度加工的理想模型系统。 具体和系统的方式。了解控制电路的基本概念 嗅球(OB)对于阐明OB神经元如何处理和代表气味是至关重要的。基本气味 OB的编码单位是肾小球模块，由一个肾小球组成，呈球形收敛 表达相同气味受体(OR)的嗅觉神经元轴突和突触后 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 从OB到皮质结构。OB表面的肾小球组织是可靠的和刻板的 在动物中，OSN或表达在确定OSN靶向和定位中起主要作用 肾小球形成。然而，M/T细胞的数量和空间分布对应于单个 肾小球模块未知。在目标1中，我将确定肾小球体积(内在)之间的关系 或因气味暴露而改变)以及对应于单个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特定气味条件反射来研究 气味引起单个肾小球的M/T细胞网络的结构变化。为了实现这些目标，我将 使用电穿孔技术专门标记与单个基因识别的肾小球相关的M/T细胞。我的 初步发现动物与动物在M/T细胞的数量和空间分布上具有相似性 在M72肾小球模块内。我的数据还显示了显著的、持续性的肾小球体积变化和 出生前和出生后早期接触气味后相关M/T细胞数量增加。我预测 在P10之前接触气味会导致M/T细胞网络发生深刻而持久的结构变化 激活的肾小球。这些结果不仅描述了基因识别的解剖学 肾小球模块，也会增加我们对感觉系统关键期的了解 解剖学的发展，从而解决了嗅觉领域的一个基本知识空白。在……里面 此外，这项工作与我对麻醉学的临床兴趣密切相关。了解基本原理 感觉系统的回路对于研究麻醉剂扰乱感觉的机制至关重要。 感知力。因此，我建议将严格的导师式研究培训、纵向临床 经验、课程安排，以及专业和领导力发展活动。知识分子，技术人员， 在这次团契培训期间磨练的专业技能将对我的 在麻醉学临床领域发展成为一名有抱负的内科科学家。

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.